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 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 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
Résumé : National audience
INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis and detecting PAH efficiently remains challenging. The DETECT study has offered in 2013 a composite screening tool for PAH. The objective of our study was to compare the indication of right heart catheterisation (RHC) as suggested by the DETECT algorithm with the decisions of a multidisciplinary team. METHODS: This prospective monocentric non-interventional study consecutively included systemic sclerosis patients when data required to apply DETECT algorithm were available. We evaluate the number of RHC as requested by this algorithm and confronted it with the indications of RHC suggested by a multidisciplinary group blinded for the result of DETECT algorithm. RESULTS: In total, 117 systemic sclerosis patients were included. When DETECT algorithm was applied to all patients, RHC was suggested by this algorithm for 70 patients, whereas only 15 indications were required by the multidisciplinary group; among those patients only 7 had PAH. When DETECT algorithm was applied only to the 42 patients with DLCO<60% and disease duration of more than 3 years, RHC was suggested for 31 patients whereas only 13 were indicated by the multidisciplinary group; among those patients only 7 had PAH. CONCLUSION: The DETECT algorithm is able to efficiently detect all PAH patients finally diagnosed by our multidisciplinary team. However, it increases by 3 the number of RHC that should be performed.
La Revue de Médecine Interne

hal-01579606
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579606
DOI : 10.1016/j.revmed.2017.04.005
PUBMED : 28545856

Éditeur(s) : HAL CCSD European Respiratory Society
Résumé : International audience
Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis. We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-Associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival. 237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046). TERT/TERC DAV were associated with specific clinical and biological features and reduced transplantfree survival. ©ERS 2016.
ISSN: 0903-1936

hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/file/Prevalence%20and%20characteristics%20of%20TERT.pdf
DOI : 10.1183/13993003.02115-2015

Éditeur(s) : HAL CCSD
Résumé : National audience
Objective of the study An estimation of burden of serious fungal diseases in France is essential data to inform public health priorities on the importance of resources and research needed on these infections. In France, precise data are available for invasive fungal diseases but estimates for several other diseases such as chronic and immunoallergic diseases are by contrast less known. Materials and methods A systematic literature search was conducted using the Web of Science Platform. Published epidemiology papers reporting fungal infection rates from France were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence, depending on the condition. Results The model predicts high prevalences of severe asthma with fungal sensitization episodes (189 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis (145/100,000) and of chronic pulmonary aspergillosis (5.24/100,000). Besides, estimated incidence for invasive aspergillosis is 1.8/100,000 annually based on classical high risk factors. Estimates for invasive mucormycosis, pneumocystosis and cryptococcosis are 0.12/100,000, 1/100,000 and 0.2/100,000, respectively. Regarding invasive candidiasis, more than 10,000 cases per year are estimated, and a much higher number of recurrent vaginal candidiasis is probable but must be confirmed. Finally, this survey was an opportunity to report a first picture of the frequency of tinea capitis in France. Conclusion Using local and literature data of the incidence or prevalence of fungal infections, approximately 1,000,000 (1.47%) people in France are estimated to suffer from serious fungal infections each year. © 2016 Elsevier Masson SAS
Journal de Mycologie Medicale

hal-01467554
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467554
DOI : 10.1016/j.mycmed.2016.11.001
PUBMED : 27887809

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.
ISSN: 0934-9723

inserm-00872789
http://www.hal.inserm.fr/inserm-00872789
DOI : 10.1007/s10096-012-1730-7
PUBMED : 22930407

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Antisynthetase 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.
Le 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.
ISSN: 0761-8425

hal-01085369
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369/file/Manifestations%20pulmonaires%20du%20syndrome%20des%20antisynth%C3%A9tases_accepted.pdf
DOI : 10.1016/j.rmr.2014.07.013

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
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 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 : National audience
INTRODUCTION:The AIRBAg study screens for bronchial obstruction in dairy farmers. We present the preliminary results after one year.METHODS:A prospective screening study based on questionnaires and electronic mini-spirometry (Néo-6(®)) that includes a representative sample of dairy farmers from the departments of Morbihan and Île-et-Vilaine in Brittany. The dairy farmers had an occupational medicine appointment and, if they demonstrated at least one marker of possible bronchial obstruction (chronic cough, chronic bronchitis, dyspnoea, wheezing, FEV1/FEV6<0.8), they were referred to a pulmonologist. The data we present here were extracted from the occupational medicine appointments because the pulmonologists' appointments are still running.RESULTS:Among the 277 dairy farmers included, 125 (45%) demonstrated "possible bronchial obstruction". The total score of the CAT questionnaire was higher in these farmers (9.1±6.2 versus 5.8±4.0; P<0.0001). In multivariate analysis markers of "possible bronchial obstruction" were eczema, manual foddering and duration of mechanical straw litter spreading.CONCLUSION:Occupational medicine appointments identified markers of "possible bronchial obstruction". We will have the complete results from AIRBAg study in 2015.
ISSN: 0761-8425

hal-01117944
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117944
DOI : 10.1016/j.rmr.2014.03.014
PUBMED : 25847201

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
To investigate the contribution of whole-body post-mortem computed tomography (PMCT) in sudden unexpected death in infants and children.METHODS:Forty-seven cases of sudden unexpected death in children investigated with radiographic skeletal survey, whole-body PMCT and autopsy were enrolled. For imaging interpretation, non-specific post-mortem modifications and abnormal findings related to the presumed cause of death were considered separately. All findings were correlated with autopsy findings.RESULTS:There were 31 boys and 16 girls. Of these, 44 children (93.6 %) were younger than 2 years. The cause of death was found at autopsy in 18 cases (38.3 %), with 4 confirmed as child abuse, 12 as infectious diseases, 1 as metabolic disease and 1 as bowel volvulus. PMCT results were in accordance with autopsy in all but three of these 18 cases. Death remains unexplained in 29 cases (61.7 %) and was correlated with no abnormal findings on PMCT in 27 cases. Major discrepancies between PMCT and autopsy findings concerned pulmonary analysis.CONCLUSIONS:Whole-body PMCT may detect relevant findings that can help to explain sudden unexpected death and is essential for detecting non-accidental injuries. We found broad concordance between autopsy and PMCT, except in a few cases of pneumonia. It is a non-invasive technique acceptable to relatives.KEY POINTS:• Whole-body post-mortem computed tomography (PMCT) is an effective non-invasive method. • Whole-body PMCT is essential for detecting child abuse in unexpected death. • There is concordance on cause of death between PMCT and autopsy. • Whole-body PMCT could improve autopsy through dissection and sampling guidance. • PMCT shows findings that may be relevant when parents reject autopsy.
ISSN: 0938-7994

inserm-01576306
http://www.hal.inserm.fr/inserm-01576306
DOI : 10.1007/s00330-012-2738-1
PUBMED : 23242003

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Sickle cell anemia (SCA or SS homozygous sickle cell disease) is an inherited blood disorder caused by single 12 nucleotide substitution in the ␤-globin gene that renders their hemoglobin (HbS) much less soluble than normal hemoglobin 13 (HbA) when deoxygenated. The polymerization of HbS upon deoxygenation is the basic pathophysiologic event leading to 14 RBC sickling, hemolysis, vasoocclusion and ultimately to chronic organ damage. The metabolic changes imposed by exercise 15 may initiate sickling and vaso-occlusive episodes. Further, in patients with SCA, exercise limitation may be related to anemia 16 or chronic complications such as pulmonary vascular disease, congestive heart failure and chronic parenchymal lung disease. 17 Few studies have investigated the cardiorespiratory responses of patients with SCA during either symptom-limited maximal 18 exercise test on cyclo-ergometer or during a six minute walk test. Therefore, patients are advised to start exercise slowly and 19 progressively, to maintain adequate hydration during and after exercise, to avoid cold exposure or sudden change in temperature, 20 and to avoid sports associated with mechanical trauma. There are, however, lack of evidence to allow practitioners to prescribe 21 an exercise program for patients with SCA, and individuals are usually encouraged to exercise on a symptom-limited basis. 22 Finally, this review will also highlight the basic principles that are often used for exercise practice and could be used for exercise 23 prescription and rehabilitation in patients with sickle cell anemia.
ISSN: 1386-0291

hal-01163966
https://hal.univ-antilles.fr/hal-01163966
DOI : 10.3233/CH-2011-1465

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: Mutations in the telomerase complex (TERT and TR) are associated with pulmonary fibrosis and frequent hematologic manifestations. The aim of this study was to characterize the prognosis of lung transplantation in patients with TERT or TR mutations. METHODS: Patients with documented TERT or TR mutations who received a lung transplant between 2007 and 2013 in France were identified via an exhaustive search of the lung transplantation network, one expert genetic laboratory, and the clinical research network on rare pulmonary diseases. RESULTS: There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary fibrosis. Median age was 50 years (range, 35-61 years) at diagnosis and 52 years (range, 37-62 years) at the time of lung transplantation. Thrombocytopenia was present in 7 patients before lung transplantation. After lung transplantation, 6 patients developed myelodysplasia and/or bone marrow failure, directly contributing to death in 4 cases. Anemia was observed in 9 patients, and neutropenia was observed in 3 patients. The median survival after lung transplantation was 214 days (range, 59-1,709 days). CONCLUSIONS: Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure. Specific recommendations should be developed for appropriate guidance regarding hematologic risk assessment before transplantation and management of the post-transplantation immunosuppressive regimen.
ISSN: 1053-2498

hal-01146848
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146848/file/Severe%20hematological%20complications%20after%20lung%20transplantation_accepted.pdf
DOI : 10.1016/j.healun.2014.11.010

Éditeur(s) : HAL CCSD
Résumé : International audience
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 extless 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
Respiration; International Review of Thoracic Diseases

hal-01239807
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01239807
DOI : 10.1159/000431380
PUBMED : 26277885

Éditeur(s) : HAL CCSD
Résumé : International audience
Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.
Revue Des Maladies Respiratoires

hal-01560287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560287
DOI : 10.1016/j.rmr.2017.03.034
PUBMED : 28552256

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

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
The Société de pneumologie de langue française defines acute exacerbation of chronic obstructive pulmonary disease (AE COPD) as an increase in daily respiratory symptoms, basically duration ≥ 48h or need for treatment adjustment. Etiology of EA COPD are mainly infectious, viral (rhinovirus, influenzae or parainfluenzae virus, coronavirus, adenovirus and respiratory syncytial virus) or bacterial (Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis). Pollutant exposure can also lead to AE COPD, such as NO2, SO2, ozone or particulates (PM10 and PM2.5). In 30% the etiology remains unknown. Differential diagnoses of AE COPD include infectious pneumonia, pneumothorax, acute heart failure and pulmonary embolism. Presences of signs of severity impose hospitalization: signs of respiratory distress, shock, acute confusion but also fragile patients, insufficient home support or absence of response to initial treatment. AE COPD treatments consist on increase in bronchodilators, chest physiotherapy, and antibiotics if sputum is frankly purulent. Systemic corticosteroids should not be systematic.Recommended dose is 0.5 mg/kg on short course (7 days). During hospitalization, oxygen supplementation and thromboprophylaxis could be prescribed. The main interest in noninvasive ventilation is persistent hypercapnia despite optimal medical management. During ambulatory management or hospitalization, clinical assessment at 48-72h is mandatory. L’exacerbation aiguë de bronchopneumopathie chronique obstructive (EA BPCO) représente un événement important dans l’histoire naturelle de la BPCO, notamment en cas d’hospitalisation. Les EA BPCO interviennent dans la gravité et l’évolution de la BPCO ; et leur prévention est un des objectifs principal des traitements de fond.
La Société de pneumologie de langue française définie l’exacerbation aiguë de bronchopneumopathie chronique obstructive (EA BPCO) comme une majoration des symptômes respiratoires au-delà des variations quotidiennes, en pratique, d’une durée ≥ 48h ou justifiant une modification thérapeutique. L’étiologie de ces EA BPCO est principalement infectieuse, virale (rhinovirus, virus influenzae et parainfluenzae, coronavirus, adénovirus et virus respiratoire syncytial) ou bactérienne (principalement Haemophilus influenzae, Streptococcus pneumoniae et Moraxella catarrhalis). Elles peuvent également résulter de l’exposition à certains polluants comme le NO2, le SO2, l’ozone et la pollution particulaire (PM10 et PM2,5). L’étiologie reste indéterminée dans près de 30 % des cas. Les diagnostics différentiels des EA BPCO incluent les pneumopathies infectieuses, les pneumothorax, les poussées d’insuffisance cardiaque et les embolies pulmonaires. La présence de signes de gravité conditionnent l’hospitalisation : signes d’insuffisance respiratoire aiguë, de choc ou de défaillance neurologique, mais aussi en cas de patient fragile, d’absence de soutien familial à domicile ou d’absence de réponse au traitement initial. Le traitement d’une EA BPCO consiste en une majoration des bronchodilatateurs, une kinésithérapie respiratoire, une antibiothérapie en cas d’expectoration franchement purulente.La prescription de corticoïdes systémiques ne doit pas être systématique. La dose recommandée est de 0,5 mg/kg sur une courte période (7 jours). Lors d’une hospitalisation, une oxygénothérapie et une thromboprophylaxie peuvent être prescrite. La ventilation noninvasiveest principalement indiquée en cas de persistance d’une hypercapnie malgré un traitement médical optimal. Que le patient soit pris en charge en ambulatoire ou en hospitalisation, une réévaluation clinique à 48-72h est indispensable.
ISSN: 0755-4982

hal-01117949
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949/file/Prise%20en%20charge%20des%20exacerbations_accepted.pdf
DOI : 10.1016/j.jeurea.2015.02.002