[Probe based confocal laser endomicroscopy in thoracic endoscopy]. / La microscopie confocale appliquée à l'endoscopie thoracique.

INTRODUCTION: Probe based confocal laser endomicroscopy (pCLE) is a new endoscopic imaging technology. It uses mini probes which can be introduced through the working channels of endoscopes. Whenever applied on the tissue of interest, they allow imaging of tissue at a cellular level. STATE OF ART: In the filed of pleuropulmonary malignancies, pCLE showed mostly its ability to guide biopsies samplings. Those results need to be validated in larger prospective studies. In interstitial lung diseases, pCLE provides information complementary to other clinical and paraclinical data. The valuability of these informations need to be investigated further, prospectively in randomized trials. In obstructive pulmonary diseases, pCLE is able to investigate the structural and functional relationships between pulmonary structures. pCLE showed good ability in the identification of acute cellular rejection after lung transplantation. PERSPECTIVES AND CONCLUSION: For the time being, pCLE is not part of routine clinical practice. The data available need to be validated in larger randomized prospective trials, before it can be recommended as a guiding tool for biopsies or as a diagnostic tool for pathologic process. New fluorophores are now available. They are specific of some molecular sequences, allowing the enhancement of specific targets within the sample studied.

[Chronic obstructive pulmonary disease. A chronic inflammatory disease]. / La bronchopneumopathie chronique obstructive. Une maladie inflammatoire chronique.

Chronic Obstructive Pulmonary Disease (COPD) is a disease caused by a chronic inflammatory response induced by the inhalation of cigarette smoke or toxic particles/gases in the airways. However, we actually know that COPD is a disease that does not only induce inflammation in lung parenchyma and bronchi, but also provokes systemic inflammation which plays a role in multiple comorbidities. Thereby, treatment of COPD should not only focus on the bronchi to relieve symptoms, improve respiratory function and reduce the rate of exacerbations, but must also be extended to the systemic effects of the disease.

: La Broncho-Pneumopathie Chronique Obstructive (BPCO) est une maladie provoquée par une réponse inflammatoire chronique suite à l'inhalation de la fumée de cigarette ou d'aérocontaminants toxiques pour les voies aériennes. Cependant, nous savons aujourd'hui que la BPCO est une maladie induisant non seulement une inflammation au niveau du parenchyme pulmonaire et des bronches, mais aussi une inflammation systémique qui peut jouer un rôle dans de multiples comorbidités. Ainsi, le traitement de la BPCO ne doit pas seulement se focaliser sur le versant bronchique dans le but de soulager les symptômes, d'améliorer la fonction respiratoire et de réduire le taux d'exacerbation, mais doit aussi s'étendre aux effets systémiques de la maladie.

[Fixed combination of budesonide, formoterol, glycopyrronium for the treatment of severe COPD : Trixeo Aerosphere®]. / Le médicament du mois. Combinaison fixe budésonide, formotérol, glycopyronium pour le traitement de la BPCO modérée à sévère : Trixeo Aerosphère®.

Here we present pharmacological and clinical properties of a new fixed triple inhaled combination including an inhaled corticoid, a long acting ?2 agonist and a long acting anticholinergic for the treatment of severe chronic obstructive pulmonary disease (COPD). Trixeo Aerosphere® is the name of this triple combination which contains 160 µg budesonide, 4,8 µg formoterol and 9 µg glycopyrronium delivered by a pMDI. As compared to a budesonide/formoterol combination, Trixeo Aerosphere® improves forced expiratory volume in the first second (FEV1). As compared to glycopyrronium/formoterol combination, Trixeo Aerosphere® reduces exacerbation rate, improved quality of life and most importantly reduces mortality with a benefit increasing with blood eosinophil count. Trixeo Aerosphere® 320/18/9.6 is delivered twice daily 2 inhalations and is indicated in moderate to severe COPD insufficiently controlled by LABA/LAMA (long-acting ?2-adrenergic receptor agonist/ long-acting ?2-muscarinic receptor agonist) or ICS/LABA (inhaled corticosteroid/long-acting ?2-adrenergic receptor agonist).

Nous présentons dans cet article les propriétés pharmacologiques et les effets cliniques d'une nouvelle triple combinaison fixe inhalée comprenant un corticoïde inhalé, un ?2 mimétique à longue durée d'action et un anticholinergique à longue durée d'action, destinée au traitement de la bronchopneumopathie chronique obstructive (BPCO) sévère. Cette combinaison qui porte le nom de Trixeo Aerosphere® regroupe, dans le même dispositif, 160 µg de budésonide, 4,8 µg de formotérol et 18 µg de glycopyrronium. Par rapport à une combinaison budésonide/formotérol, le Trixeo Aerosphere® améliore la valeur du volume expiratoire maximum par seconde (VEMS). Par rapport à une combinaison formotérol/glycopyrronium, le Trixeo Aerosphere® réduit la fréquence des exacerbations et réduit la mortalité avec un bénéfice qui augmente avec le taux des éosinophiles circulants. Le Trixeo Aerosphere®, à la dose de 2X2 bouffées/24h, est indiqué dans le traitement des patients BPCO modérés à sévères insuffisamment contrôlés par une bithérapie LABA/LAMA (long-acting ?2-adrenergic receptor agonist/ long-acting ?2-muscarinic receptor agonist) ou ICS/LABA (inhaled corticosteroid/long-acting ?2-adrenergic receptor agonist).

[Liver transplantation for hepatopulmonary syndrome complicating cirrhosis]. / Transplantation hépatique pour syndrome hépatopulmonaire compliquant une cirrhose.

Hepato-pulmonary syndrome (HPS) is a pulmonary vascular complication of cirrhosis quite frequent but often under-diagnosed, and characterized by intra-pulmonary capillary and pre-capillary vascular dilatations that may lead to severe hypoxemia. HPS is often asymptomatic but may induce a progressive dyspnea. HPS diagnosis is based on arterial gasometry that proves the hypoxemia and contrast-enhanced echo-cardiography revealing the vascular dilatations. Screening of HPS is recommended in every cirrhotic patient complaining of dyspnea or in every liver transplantation candidate. Indeed, the only effective treatment of HPS is liver transplantation; HPS patients receive exception-points in the MELD (Model for End-Stage Liver Disease) liver allocation score. The authors report herein the case of a 39-year-old male patient with a cirrhosis of unknown origin complicated by HPS which appeared as a disabling dyspnea. This patient underwent liver transplantation a year after HPS diagnosis and recovered completely.

Le syndrome hépatopulmonaire est une complication vasculaire pulmonaire de la cirrhose relativement fréquente et sous-diagnostiquée, caractérisée par des vasodilatations capillaires et pré-capillaires intrapulmonaires pouvant entraîner une hypoxémie sévère. Souvent asymptomatique, ce syndrome se révèle le plus souvent par une dyspnée d'apparition progressive. Le diagnostic est réalisé par une gazométrie artérielle prouvant l'hypoxémie et une échographie cardiaque de contraste démontrant l'existence de vasodilatations intrapulmonaires. Le dépistage du syndrome hépatopulmonaire est préconisé chez tout patient atteint de cirrhose présentant de la dyspnée et chez tout patient candidat à une greffe hépatique. En effet, le seul traitement efficace est la transplantation hépatique, et ces patients bénéficient d'ailleurs de points d'exception dans le calcul du score de MELD («Model for End-Stage Liver Disease¼). Nous rapportons ici le cas d'un patient de 39 ans atteint d'une cirrhose d'origine indéterminée compliquée d'un syndrome hépatopulmonaire qui s'est révélé par une dyspnée devenue rapidement invalidante. Ce patient a pu bénéficier d'une transplantation hépatique un an après le diagnostic de syndrome hépatopulmonaire, permettant ainsi une guérison complète tant sur plan hépatique que pulmonaire.

[Empyema and subacute invasive aspergillosis following drowning]. / Cas clinique.Empyème et aspergillose invasive subaiguë dans les suites d'une inhalation lors d'une noyade.

Empyema and subacute invasive aspergillosis are rare pathologies that should not be overlooked because of the need for early treatment and a different management of bacterial infections which are more frequent. We report the case of a 75-year-old man with subacute invasive aspergillosis and an empyema following drowning and cardiopulmonary arrest.

L'empyème à Aspergillus fumigatus et l'aspergillose invasive subaiguë sont des pathologies rares à ne pas méconnaître au vu de la nécessité d'un traitement précoce et d'une prise en charge différente des infections pleuropulmonaires bactériennes qui sont plus fréquentes. Nous rapportons le cas d'un patient de 75 ans présentant une aspergillose invasive subaiguë, associée à un empyème, dans les suites d'une noyade avec arrêt cardiopulmonaire.

[Medical thoracoscopy in respiratory medicine: The Liège University Hospital experience]. / La thoracoscopie médicale en pratique pneumologique : expérience du CHU de Liège.

INTRODUCTION: The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity. METHOD: We report the retrospective evaluation, the efficacy and the observed complications in 1024 medical thoracoscopies undertaken in the University Hospital of Liège between 2000 and 2017. RESULTS: In total, 100 pneumothoraces and 400 benign and 501 malignant pleural diseases were identified. The main indication for thoracoscopy remains the diagnosis of an exudative, lymphocytic pleural effusion of unknown aetiology after thoracocentesis. The diagnostic sensibility of thoracoscopy was 99.2% in distinguishing benign from malignant pleural disease. Talc pleurodesis was performed in 69.5% of the total population and in 66.1% of pleural effusions or thickening. Failure of pleurodesis was observed in 11% of the patients with recurrent pneumothorax and in 7.8% of neoplastic pleural effusion. We report a mortality of 0.6% in the 30 days post procedure, long duration of drainage in 8.3% and serious complications in 4.7%. In 22/1024 (2.1%) thoracoscopic evaluation was not feasible because of dense pleural fibrosis. CONCLUSION: Medical thoracoscopy is a safe, well-tolerated procedure with high accuracy in the diagnostic and therapeutic management of pleural disease.

[Bronchial thermoplasty in the management of severe asthma : retrospective analysis of 10 cases treated at academic hospital of Liège]. / Thermoplastie bronchique dans le traitement de l'asthme sévère. Analyse rétrospective de 10 cas traités au CHU de Liège.

As treating severe forms of asthma represents a medical and economical challenge, research for new therapies in this area is extensive and expansive. Recently, bronchial thermoplasty (BT) - ie. bronchoscopic procedure delivering a thermic form of energy through radiofrequency to the bronchi, in order to interfere with the components of the smooth muscle layer - arose as a promising technique. Our study followed the path of 10 patients from CHU Liège (University Hospital), who underwent this procedure in a context of severe asthma. We compared clinical and spirometric and treatment data in patients at 0 - 6 and 12 months post-procedural intervals, in order to determine whether thermoplasty had been improving asthma. Overall, we observed a stabilization and possibly a clinical improvement while reducing the total amount of exacerbation rate, and the burden of maintenance oral corticoids.

En raison du défi médico-économique que représente le traitement des formes sévères d'asthme, les recherches concernant de nouvelles thérapies dans ce domaine sont multiples et variées. Récemment, la thermoplastie bronchique - correspondant à un acte bronchoscopique permettant de délivrer une énergie par radiofréquence au niveau des bronches, afin d'interférer avec les composants de la couche musculaire lisse - s'annonçait comme une procédure prometteuse. Nous avons étudié 10 patients, suivis au CHU de Liège dans un contexte d'asthme sévère, et ayant bénéficié de cette technique. Nous avons comparé des données cliniques, spirométriques et thérapeutiques aux intervalles de 6 et 12 mois après procédure, afin de de déterminer si celle-ci avait été bénéfique sur leur pathologie asthmatique. Globalement, nous observons une stabilisation, voire une amélioration clinique, avec, notamment, une diminution des exacerbations, tout en réduisant la charge en corticoïdes systémiques.

First report of probe based confocal laser endomicroscopy during medical thoracoscopy.

Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique, generating fluorescent light emission from the tissue of interest and allowing in vivo live imaging at a cellular level ("optical biopsies"). To the best of our knowledge, this article is the first to present pCLE images during medical thoracoscopy. We present here 3 different patients referred for various health problems. A precise description of pleural cavity pCLE images after intravenous fluorescein injection (a fluorophore) together with corresponding macroscopical and histological studies is performed. This led to the diagnosis of normal pleura in one case, carcinomatous pleuritis in another case and a malignant mesothelioma in the third case. We believe that optical biopsies could help clinicians to make an early diagnosis, thereby allowing rapid therapeutic intervention (talc pleurodesis for example). Furthermore, it could help to guide biopsies when affected zones are not obvious to macroscopic examination. In a near future, new fluorophores could be developed to stain some pathophysiological processes, therapeutic targets, or enzymes activities bringing new insights in endoscopic pleural disease work-up.

IgG4-related pleural disease in a patient with a history of unknown origin acute pancreatitis: a case report and review of the literature.

Immunoglobulin G4-related disease is a rare autoimmune systemic disease with the capability of involving every organ. The disease is microscopically defined by a diffuse tissular inflammation with an infiltration of IgG4 positive plasma cells in the affected organs. IgG4 disease has an increasing incidence in the last few years with a growing interest in its pathophysiology still misunderstood to date. Despite the growing recognition of this pathology, the literature still does not allow to propose a simple diagnostic algorithm. In this article, we present a case of a 56-year-old man with a history of unknown etiology acute pancreatitis and a unilateral pleural effusion.

[Invasive diagnostic techniques for diffuse interstitial pneumopathies]. / Comment j'explore... Techniques diagnostiques invasives des pneumopathies interstitielles diffuses.

Interstitial lung diseases represent a very heterogeneous group of diseases mainly affecting connective lung tissue even if alveolar space may sometimes be involved. The identification of their etiology is the key stage in their management. It requires the integration of anamnestic, clinical, biological, radiological data and, sometimes relies on, cytology or histology. In this review, we assess the contribution and feasibility of the different invasive techniques used for interstitial lung disease diagnosis. In particular we focus on the yield of lung endoscopy in casting light on the multidisciplinary confrontation, which is the gold standard of the interstitial lung disease care management.

Les pneumopathies interstitielles diffuses constituent un groupe très hétérogène de pathologies respiratoires qui affectent le parenchyme pulmonaire et qui se manifestent radiologiquement par des opacités interstitielles, même si une atteinte alvéolaire peut y être associée. L'identification de leur étiopathologie constitue une étape clé dans leur prise en charge thérapeutique. Elle nécessite l'intégration de données anamnestiques, cliniques, biologiques, radiologiques et parfois cyto/histologiques. Le but de cette revue est de préciser l'apport respectif et la faisabilité des diverses techniques semi-invasives et invasives d'exploration d'une pneumopathie interstitielle diffuse. En particulier, l'endoscopie pulmonaire fournit des éléments qui permettent d'éclairer la confrontation multidisciplinaire, cette dernière étant le gold standard de la prise en charge de ces pneumopathies.

[Comparison between chylothorax and pseudochylothorax]. / Chylothorax et pseudochylothorax: contraste á partir de deux observations.

We report two cases of lipidic pleural effusion: an arthritis-associated pseudochylothorax and a chylous pleural effusion in a HIV seropositive patient. The incidence of lipidic pleural effusions is low, especially for pseudochylothorax. We review their clinical characteristics and management.

[ENDOSCOPIC LUNG VOLUME REDUCTION IN PULMONARY EMPHYSEMA]. / RÉDUCTION ENDOSCOPIQUE DU VOLUME PULMONAIRE DANS L'EMPHYSÈME PULMONAIRE.

Emphysema is characterized by an irreversible alveolar destruction, a progressive lung hyperinflation and a dysfunction of respiratory muscles. It induces a respiratory functional limitation and a decrease of quality of life. Endoscopic lung volume reduction represents a potential alternative to surgical treatments for advanced heterogeneous emphysema without concomitant surgical morbidity. The different bronchoscopic systems for lung volume reduction currently under evaluation are presented.

[Pleurisy of unexpected etiology: a foreign body within the pleural cavity]. / Pleurésies d'étiologie inattendue: le corps étranger au sein de la cavité pleurale.

Following three brief clinical reports, we review the literature concerning a rare cause of exudative pleural effusion: the presence of a foreign body in the pleural cavity. Frequently iatrogenical, this rare etiology of pleural effusion must be envisaged when this complication develops after any invasive peri-thoracic surgery and must be included in the differential diagnosis of recurrent pleural effusions. These effusions have a favorable prognosis after withdrawal of the foreign body.

[Thoracic ultrasound: the pneumologist's new stethoscope]. / Comment j'explore.... L'echographie thoracique: le nouveau stéthoscope du pneumologue.

We now have access to a large library of publications validating transparietal thoracic echography in various clinical situations. Parietal lesions, including osteolysis, can be detected and biopsied during the thoracic ultrasound (TUS) examination. To evaluate the parietal extension of lung cancers, TUS has proved superior to tomodensitometry. Pleural effusions can be easily diagnosed and aspirated. Pneumothoraces can be detected using well defined lung artifacts with a high frequency probe. Pleural and peripheral lung nodules can be detected and biopsied with real time visualization; the procedure is safe and accurate. Lung consolidations with a pleural contact can be diagnosed; this is particularly useful for pregnant women. In conclusion, TUS is a precious diagnostic tool for chosen applications, and can help to guide interventional procedures. The portable devices are also very useful for bedridden patients or for out of hospital use.

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease caused by repeated exposure to noxious gases or particles. It is now recognized that the disease also features systemic inflammation. The purpose of our study was to compare airway and systemic inflammation in COPD to that seen in healthy subjects and to relate the inflammation with the disease severity. METHODS: Ninety-five COPD patients, encompassing the whole severity spectrum of the disease, were recruited from our outpatient clinic and rehabilitation center and compared to 33 healthy subjects. Induced sputum and blood samples were obtained for measurement of inflammatory cell count. Interleukin (IL)-4, IL-6, IL-10, TNF-α and IFN-γ produced by 24h sputum and blood cell cultures were measured. RESULTS: Compared to healthy subjects, COPD exhibited a prominent airway neutrophilic inflammation associated with a marked IL-10, IL-6 and TNF-α release deficiency that contrasted with a raised IFN-γ production. Neutrophilic inflammation was also prominent at blood level together with raised production of IFN-γ, IL-10 and TNF-α. Furthermore, sputum neutrophilia correlated with disease severity assessed by GOLD stages. Likewise the extent of TNF-α release from blood cells also positively correlated with the disease severity but negatively with that of sputum cell culture. Blood release of TNF-α and IL-6 negatively correlated with body mass index. Altogether, our results showed a significant relationship between cellular marker in blood and sputum but poor relationship between local and systemic release of cytokines. CONCLUSIONS: COPD is characterized by prominent neutrophilic inflammation and raised IFN-γ production at both bronchial and systemic level. Overproduction of TNF-α at systemic level correlates with disease severity and inversely with body mass index.

[Endobronchial ultrasonography: a novel technique for investigation of the mediastinum]. / Echographie endobronchique: une nouvelle technique d'investigation du médiastin.

Mediastin pathology includes primary lesion and lymph node invasion. The exploration of this anatomical region remains difficult and even hazardous, particularly to obtain histological biopsies. No invasive diagnostic exploration (thorax tomodensitometry and positron emission tomography) allows a histological precision, so mediastinoscopy remains the gold standard in the mediastinum investigation. However, it is not deprived of risk. Recently, guided biopsies and real-time transbronchial needle aspiration by endobronchial ultrasonography (EBUS) have been shown to increase the diagnostic yield over conventional bronchoscopic techniques. Therefore, EBUS is a suitable alternative to mediastinoscopy in the diagnosis of pulmonary or extra-thoracic malignancy, in the staging of mediastinal lymphadenopathy, and in the evaluation of mediastinal response after induction therapy. In the present paper, we present this new diagnostic approach and clarify the current indications of EBUS.

[Giant cell arteritis revealed by scalp necrosis]. / Le cas clinique du mois. Nécrose du cuir chevelu révélatrice d'une artérite a cellules géantes (maladie de Horton).

Scalp necrosis is an uncommon manifestation of giant cell arteritis (GCA). In this paper, we report our experience with a 78-year old woman in whom extensive scalp necrosis developed as a complication of GCA. A left frontal defect (7 X 4 cm) involving full-thickness scalp was observed. The necrosis extended deeply, involving the epicranium and the outer table of the skull. The therapeutic approach included corticotherapy, anticoagulation and wound care. Severe wound infection (osteitis, subgaleal abscess) occurred, requiring prolonged antibiotherapy. Second intention healing was obtained using a conservative approach. During the healing process, areas of neovascularization developed beneath the exposed part of the outer table and the necrotic bone underwent resorption.

[Exhaled nitric oxide: a new biomarker for respiratory pathologies]. / Le monoxyde d'azote exhalé: un nouveau biomarqueur des pathologies respiratoires.

There has been a growing interest for exhaled biomarkers. We review studies examining NO as a potential marker of airway inflammation, enabling noninvasive repeated monitoring of airway inflammation. The measurement technique has been standardized. We have determined the local normal levels for the Liège region. The exhaled NO level is elevated in asthma, and can predict asthma exacerbation. Exhaled NO has a value for the diagnosis of cystic fibrosis and primary ciliary dyskinesia.

Effects of a progestogen on normal human breast epithelial cell apoptosis in vitro and in vivo.

Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis. Both the follicular and luteal phases of the menstrual cycle are characterized by proliferation, whereas apoptosis occurs only at the end of the latter phase. In this study, we observed that the withdrawal of a synthetic progestin (nomegestrol acetate or NOMAC), but not continuous treatment with it, induced apoptosis of normal human breast epithelial cells in vitro and in women who applied NOMAC gel to their breasts. Furthermore, this apoptotic response was specific to normal breast cells, since withdrawal of NOMAC did not induce apoptosis of tumoral T47D cells in vitro or of fibroadenoma cells in women. These observations open up new perspectives in the prevention of hyperplasia and breast cancer.