[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).

[Trimbow® : twice-daily triple combination for the treatment of COPD]. / Le médicament du mois Trimbow® ou triple association bronchodilatatrice et anti-inflammatoire en aérosol dans la broncho-pneumopathie chronique obstructive.

Single-inhaler triple therapy in extrafine solution combining an inhaled corticostéroid (ICS), the dipropionate of beclométasone, a long acting ß2-agonist (LABA), the fumarate of formoterol and an long-acting muscarinic antagonist (LAMA), the bromide of glycopyrronium, was developed for the treatment of the chronic obstructive pulmonary disease (COPD). Trimbow® is the first triple therapy in spray with fixed dose and containing 3 pharmacological agents (LABA-LAMA-ICS). Clinical trials show that Trimbow® improves numerous parameters such as the respiratory function, the quality of life, the symptoms and the rate of moderate to severe exacerbations while being tolerated well. These results justify its use in severe and very severe COPD with exacerbations in spite of treatment by LABA-LAMA or LABA-ICS. In this article, we present a brief synthesis of the main recent clinical trials on Trimbow®, its comparison with other pharmacological agents/associations regularly used in the treatment of COPD, as well as some practical information on its use in routine.

Une triple association fixe en solution extrafine comprenant un corticostéroïde inhalé (CSI), le dipropionate de béclométasone, un ?2-agoniste à effet prolongé (LABA), le fumarate de formotérol, et un antagoniste muscarinique à action prolongée (LAMA), le bromure de glycopyrronium, a été développée pour le traitement de la broncho-pneumopathie chronique obstructive (BPCO). Le Trimbow® est ainsi la première trithérapie en aérosol à dose fixe et contenant trois agents pharmacologiques (LABA-LAMA-CSI). Les études cliniques montrent que le Trimbow® améliore de nombreux paramètres tels que la fonction respiratoire, la qualité de vie, les symptômes et le taux d'exacerbations modérées à sévères, tout en étant bien toléré. Ces résultats justifient son utilisation dans la BPCO sévère à très sévère, avec exacerbations en dépit d'un traitement par LABA-LAMA ou LABA-CSI. Dans cet article, nous présentons une brève synthèse des principales études cliniques récentes sur le Trimbow®, sa comparaison avec d'autres agents/associations pharmacologiques régulièrement utilisés dans le traitement de la BPCO, ainsi que quelques informations pratiques sur son utilisation en routine.

[Reducing COPD exacerbations : a challenge in 2017]. / Réduction des exacerbations dans la bronchopneumopathie chronique obstructive : défi en 2017.

Chronic Obstructive Pulmonary Disease (COPD) is the 4th leading cause of death in our country. Exacerbations play a major role in the course of the disease. Their consequences are multiple : accelerated decline in lung function, deterioration in patients’ quality of life and well-being, decreased physical activity, increased morbidity and mortality related to COPD, significant economic implications on health budgets and workplace absenteeism. Reducing the number of exacerbations in patients with COPD therefore represents a major challenge in the treatment of this disease. In this article, we underline the importance of these exacerbations and review the therapeutic means available in 2017 to prevent them.

La bronchopneumopathie chronique obstructive (BPCO) représente la 4ème cause de mortalité dans nos pays industrialisés. Les exacerbations jouent un rôle majeur dans le décours de la maladie. Leurs conséquences sont multiples : déclin accéléré de la fonction respiratoire, détérioration de la qualité de vie et du bien-être des patients, perte de l'activité physique, augmentation de morbidité et de mortalité relatives à la BPCO, implications économiques significatives sur les budgets de la santé et dans l'absentéisme au travail. Réduire le nombre d'exacerbations chez les patients BPCO représente donc un enjeu capital dans le traitement de la maladie. Dans cet article, nous rappelons l'importance de ces exacerbations et les moyens thérapeutiques mis à notre disposition en 2017 pour les prévenir.

[How i treat a patient with idiopathic pulmonary fibrosis]. / Comment je traite une fibrose pulmonaire idiopathique.

Idiopathic pulmonary fibrosis (IPF) is a rare disorder of unknown origin, which is associated with a high mortality and whose incidence has been increasing for several years. Nowadays there are two anti-fibrotic therapies (pirfenidone - nintedanib) known to reduce significantly the decline in respiratory function tests of patients suffering from this condition. The only curative therapeutic option remains the pulmonary transplantation whose accessibility remains limited. Pulmonary rehabilitation is also central in the treatment of patients. A major challenge for patients remains early and aggressive management to reduce as early as possible the evolution towards severe pulmonary fibrosis.

La fibrose pulmonaire idiopathique (FPI) est une maladie rare d'étiopathogénie encore mal connue et d'incidence croissante depuis plusieurs années. La mise récente sur le marché de deux traitements anti-fibrotiques (pirfénidone ­ nintédanib) a permis de réduire, de manière significative, le déclin de la fonction respiratoire des patients souffrant de cette pathologie. La seule option thérapeutique à visée curative est la transplantation pulmonaire ont l'accessibilité reste limitée. La revalidation pulmonaire est, quant à elle, également centrale dans la prise en charge. L'enjeu majeur pour ces patients est une prise en charge précoce et agressive afin de limiter l'évolution de la fibrose pulmonaire.

[Diagnosis and treatment of hereditary angioedema: clinical illustration and brief literature review]. / Diagnostic et traitement des oedèmes angioneurotiques héréditaires: illustration clinique et brève revue de la literature.

Hereditary angio-oedema is an autosomal dominant transmitted disease that is characterized by swellings of the subcutaneous or mucosal tissues. The edematous manifestations develop over a few hours and disappear spontaneously in a few days. This disease, which is due to an excess of bradykinine, a peptide that induces vasodilatation and increases vascular permeability, is different from angioedema mediated by histamine (frequently accompanied by urticaria). This difference explains the inefficiency of antiallergic therapies to treat the crises. This condition, although rare, is important to know because it is potentially lethal if the edema leads to laryngeal obstruction. After the report of a clinical example, this paper will consider the pathophysiology and the classification of angio-oedema without urticaria. New therapeutic recommendations for the treatment of hereditary angio-oedema will also be considered.

[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.

Multistep Micellization of Standard Surfactants Evidenced by Second Harmonic Scattering.

Processes involving in solution a reduced number of molecules are difficult to identify and characterize. Here, we show that micellization of standard surfactants, namely sodium dodecyl sulfate and trimethyl tetradecyl ammonium bromide, two nonefficient compounds for quadratic nonlinear optics, can be investigated by second harmonic scattering (SHS). In particular, the formation of aggregates at concentrations smaller than the critical micellar concentration is evidenced through a nonmonotonic behavior of the SHS intensity as a function of the surfactant concentration. A simple model based on chemical equilibria between monomers and micelles is proposed to account for the experimental observations. Signature of long-range molecular orientation correlation is revealed by polarization resolved experiments and is discussed regarding micellization and charge-induced effects.

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.