Lung progenitors from lambs can differentiate into specialized alveolar or bronchiolar epithelial cells.

26International audienceBACKGROUND: Airways progenitors may be involved in embryogenesis and lung repair. The characterization of these important populations may enable development of new therapeutics to treat acute or chronic lung disease. In this study, we aimed to establish the presence of bronchioloalveolar progenitors in ovine lungs and to characterize their potential to differentiate into specialized cells. RESULTS: Lung cells were studied using immunohistochemistry on frozen sections of the lung. Immunocytochemistry and flow cytometry were conducted on ex-vivo derived pulmonary cells. The bronchioloalveolar progenitors were identified by their co-expression of CCSP, SP-C and CD34. A minor population of CD34pos/SP-Cpos/CCSPpos cells (0.33% +/- 0.31) was present ex vivo in cell suspensions from dissociated lungs. Using CD34 magnetic positive-cell sorting, undifferentiated SP-Cpos/CCSPpos cells were purified (>80%) and maintained in culture. Using synthetic media and various extracellular matrices, SP-Cpos/CCSPpos cells differentiated into either club cells (formerly named Clara cells) or alveolar epithelial type-II cells. Furthermore, these ex vivo and in vitro derived bronchioloalveolar progenitors expressed NANOG, OCT4 and BMI1, specifically described in progenitors or stem cells, and during lung development. CONCLUSIONS: We report for the first time in a large animal the existence of bronchioloalveolar progenitors with dual differentiation potential and the expression of specialized genes. These newly described cell population in sheep could be implicated in regeneration of the lung following lesions or in development of diseases such as cancers

Right-to-left shunt with hypoxemia in pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Hypoxemia is common in pulmonary hypertension (PH) and may be partly related to ventilation/perfusion mismatch, low diffusion capacity, low cardiac output, and/or right-to-left (RL) shunting.</p> <p>Methods</p> <p>To determine whether true RL shunting causing hypoxemia is caused by intracardiac shunting, as classically considered, a retrospective single center study was conducted in consecutive patients with precapillary PH, with hypoxemia at rest (PaO₂< 10 kPa), shunt fraction (Qs/Qt) greater than 5%, elevated alveolar-arterial difference of PO₂(AaPO₂), and with transthoracic contrast echocardiography performed within 3 months.</p> <p>Results</p> <p>Among 263 patients with precapillary PH, 34 patients were included: pulmonary arterial hypertension, 21%; PH associated with lung disease, 47% (chronic obstructive pulmonary disease, 23%; interstitial lung disease, 9%; other, 15%); chronic thromboembolic PH, 26%; miscellaneous causes, 6%. Mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance were 45.8 ± 10.8 mmHg, 2.2 ± 0.6 L/min/m², and 469 ± 275 dyn.s.cm^-5, respectively. PaO₂in room air was 6.8 ± 1.3 kPa. Qs/Qt was 10.2 ± 4.2%. AaPO₂under 100% oxygen was 32.5 ± 12.4 kPa. Positive contrast was present at transthoracic contrast echocardiography in 6/34 (18%) of patients, including only 4/34 (12%) with intracardiac RL shunting. Qs/Qt did not correlate with hemodynamic parameters. Patients' characteristics did not differ according to the result of contrast echocardiography.</p> <p>Conclusion</p> <p>When present in patients with precapillary PH, RL shunting is usually not related to reopening of patent <it>foramen ovale</it>, whatever the etiology of PH.</p

Professional Exposure to Goats Increases the Risk of Pneumonic-Type Lung Adenocarcinoma: Results of the IFCT-0504-Epidemio Study

Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC. We performed a multicenter case-control study recruiting patients with P-ADC as cases and patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356-item questionnaire was built to evaluate exposure to livestock. A total of 44 cases and 132 controls were included. At multivariate analysis, P-ADC was significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95% confidence interval (CI): 1.32–7.87, p = 0.010), never- smoker status (OR = 3.57, 95% CI: 1.27–10.00, p = 0.015), personal history of extra-thoracic cancer before P-ADC diagnosis (OR = 3.43, 95% CI: 1.10–10.72, p = 0.034), and professional exposure to goats (OR = 5.09, 95% CI: 1.05–24.69, p = 0.043), as compared to other subtypes of lung cancer. This case-control suggests a link between professional exposure to goats and P-ADC, and prompts for further epidemiological evaluation of potential environmental risk factors for P-ADC

Protocol for the EARCO Registry : a pan-European observational study in patients with α1-antitrypsin deficiency

Rationale and objectives Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of patients with AATD. Study design and population The EARCO Registry is a non-interventional, multicentre, pan-European, longitudinal observational cohort study enrolling patients with AATD. Data will be collected prospectively without interference/modification of patient's management by the study team. The major inclusion criterion is diagnosed severe AATD, defined by an AAT serum level <11 µM (50 mg·dL−1) and/or a proteinase inhibitor genotype ZZ, SZ or compound heterozygotes or homozygotes of other rare deficient variants. Assessments at baseline and during the yearly follow-up visits include lung function testing (spirometry, body plethysmography and diffusing capacity of the lung), exercise capacity, blood tests and questionnaires (symptoms, quality of life and physical activity). To ensure correct data collection, there will be designated investigator staff to document the data in the case report form. All data will be reviewed by the EARCO database manager. Summary The EARCO Registry aims to understand the natural history and prognosis of AATD better with the goal to create and validate prognostic tools to support medical decision-making

Immunité de greffe en transplantation pulmonaire

National audienceIntroduction Lung transplantation is an effective treatment for end-stage respiratory failure, however immunological mismatch poses a major threat to graft function. State of the art An inflammatory process within the lung is initiated at the time of brain death of the donor which, even in the absence of rejection or infection, persists in the recipient after transplantation. Although immuno-suppressive therapy is able to control the cellular immune response, alveolar macrophages remain in an activated state and interactions between T cells and epithelial cells continue. Acute rejection is triggered by T cell activation with an amplification of the inflammatory process associated with mononuclear cells infiltration. The major complication of pulmonary transplantation is bronchiolitis obliterans, a pan-bronchitic process due in part to a chronic rejection process arising from the interactions between epithelial and immune cells. This immune process results in progressive tissue remodelling. Viral infections may influence pulmonary transplantation by interacting directly with the immune system; infections due to cytomegalovirus and common respiratory viruses may play a role in the long term decline of graft pulmonary function. Perspectives Concepts in lung transplantation immunology will evolve in forth-coming years as induction of microchimerism in the recipient is developed and/or organs from genetically modified porcine donors become available. Conclusion Improvements in immunosuppressive regimens are needed to reduce the risk of bronchiolitis obliterans in the transplanted lung.Introduction La greffe pulmonaire est un traitement efficace l'insuffisance respiratoire terminale ; le conflit immunologique en complique la prise en charge. Etat des connaissances Le poumon greffé est le site d'un phénomène inflammatoire initié probablement dès l'état de mort cérébrale du donneur, et persistant tout au long de la vie du receveur, même en l'absence de phénomène de rejet ou d'infection. Quoique les traitements immunosuppresseurs soient capables de diminuer la réponse immune cellulaire, il existe un état d'activation des macrophages alvéolaires ainsi que des interactions permanentes entre cellules épithéliales et lymphocytes T. Le rejet aigu est initié par une activation des lymphocytes T avec amplification du phénomène inflammatoire par domiciliation des cellules mononucléées. L'évolution de la greffe pulmonaire est marquée par le risque de développement d'une panbronchite appelée « syndrome de bronchiolite oblitérante » correspondant en partie à un phénomène de rejet chronique, marquée par des interactions permanentes entre cellules épithéliales et cellules immunitaires ; il semble que progressivement les phénomènes immunologiques fassent la place à un remodelage tissulaire. Les infections virales interviennent dans l'évolution des greffés pulmonaires en raison des interactions importantes avec le système immunitaire. Perspectives L'immunologie de la transplantation pulmonaire va évoluer, dans les années à venir vers la possibilité d'établir un état de microchimérisme du receveur et d'induire ainsi une tolérance. Conclusion La modification des protocoles d'immunosuppression est susceptible de diminuer le risque du « syndrome de bronchiolite oblitérante »

Évaluer la recherche

Mornex, J-FArch Pediatr. 2011 Mar 31.National audienc

Enseignement magistral : Intérêt potentiel de son intégration aux stages hospitaliers et de la réalisation de contrôles de connaissance impromptus

Contexte : Le cours magistral est l'une des modalités essentielles de la formation médicale initiale dans notre université. But : Évaluer l'intérêt potentiel de son intégration aux stages hospitaliers et de la réalisation de contrôles de connaissance impromptus. Méthode : Les mêmes enseignants ont assuré l'enseignement de la pneumologie simultanément pour deux Unités de Formation et de Recherche (UFR). Seuls les étudiants de l'UFR1 bénéficiaient d'un enseignement dispensé parallèlement aux stages hospitaliers (« intégré »), et d'un contrôle impromptu pris en compte dans la note globale. L'assiduité et les résultats à l'examen final ont été comparés entre 33 étudiants de l'UFR1, soit la moitié de l'effectif des étudiants de cette UFR, et 72 étudiants de l'UFR2, soit la totalité de l'effectif de cette UFR, qui ont suivi le même enseignement magistral et la même évaluation certifiante. Résultats : Les étudiants de l'UFR1 étaient significativement plus assidus, ont obtenu plus souvent une note supérieure à la moyenne, et ont obtenu une note moyenne plus élevée que ceux de l'UFR2. Ces différences étaient observées aussi bien pour la note globale que pour chacune des sous-épreuves qui la constituent. Conclusion : Malgré l'existence de biais méthodologiques, cette étude est en faveur de l'utilité d'intégrer les cours magistraux et le stage hospitalier, et d'appliquer une mesure d'incitation à l'assiduité et au travail personnel régulier, telle que le contrôle impromptu, en formation médicale initiale

[The alpha-1 antitrypsin deficiency: advances in knowledge and unsolved questions]

International audienc

Retroviral infections in sheep and the associated diseases

Current issues in Sheep Health and WelfareInternational audienceRetroviruses are RNA viruses widely distributed in most vertebrate and in many non-vertebrate species. Among the retrovirus family, small ruminant lentiviruses (SRLV), Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) infect small ruminants. JSRV and ENTV are oncogenic retroviruses responsible for pulmonary and nasal adenocarcinomas, respectively, which can lead to the death of the animals in few weeks or months. SRLV are non-oncogenic and replication-competent lentiviruses, related to human immunodeficiency virus (HIV). SRLV are responsible for slowly evolving progressive degenerative diseases leading to the death of the host after few months or years. These viruses are transmitted through the colostrum or milk and aerosolization of infectious particles. This review focuses on the biology of the small ruminant retrovirus and on the main mechanisms of disease induction