Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Reproducibility of pulmonary function tests in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune disease in which interstitial lung disease (ILD) is the leading cause of morbidity and mortality. Clinical management of the lung disease is mainly based on pulmonary function testing (PFT) and their changes over time. Little is known about the reproducibility of PFT testing in SSc patients. The aim of this study was to assess the test-retest reliability and reproducibility of PFTs in SSc patients with or without ILD over 30 days in order determine the potential physiologic variation over the time. We performed prospective observational study of SSc patients. The FVC, FEV1/FVC ratio, DLCO and KCO parameters were assessed in this population at four different timepoints; T0 (time 0) and H3 (T0 + 3 h) defined test-retest reliability, D15 (T0 + 15 days) and D30 (T0 + 30 days) for reproducibility. A mixed linear model was used to test the effect of time (and therefore reproducibility) on patients and we looked for an interaction. We included 25 SSc patients divided in two groups, 14 with ILD and 11 non-ILD. Interactions between time and group were not significant and were not reported. Time and group did not significantly influence the different measures of the PFT: FVC [p values time and group effect respectively (0.33; 0.34)], FEV1/FVC ratio (0.093; 0.056) and DLCO (0.99; 0.13) in the ILD and non ILD group (Table S2). The analyse with interactions between time and group were not significant and are not reported. We also used a Bland Altman test to assess reproducibility for FVC (L) and DLCO (mMKpa/min/L), Figs. 1 and 2 respectively. The measurements were therefore reproducible over time and in each group. PFT parameters are reproducible over time in a clinically stable population of SSc (no significant effect of the time T0, H3, D15 and D30) and there is no significant distinction between patients with ILD and no ILD. These respiratory functional data can further underline their use in clinical practice.

[Probiotics in asthma treatment]. / Les probiotiques dans le traitement de l'asthme.

Asthma is the most prevalent chronic inflammatory airway disease worldwide. The gut microbiota possesses an important link with the development of the immunity in youth and a dysregulation of the gut flora was implicated in the asthmatic disease emergence. Moreover, a dysregulation of the intestinal microbiota exists in asthmatic individual. Probiotics are micro-organisms that can regulate our microbiome conferring potential beneficial effects on health. Thereby, their use in asthma prevention and treatment is attractive and could lead to new therapeutic perspectives. Indeed, they are well tolerated and safe and possess anti-inflammatory and immunoregulatory properties. This article is intended to update the current state of knowledge regarding the use of probiotics in the context of asthma.

: L'asthme est la maladie respiratoire chronique inflammatoire la plus prévalente dans le monde. Le microbiote intestinal est reconnu pour être intimement lié avec le développement de l'immunité dans le jeune âge et un dérèglement de cette flore intestinale a été impliqué dans l'apparition de la maladie asthmatique. De plus, une dérégulation du microbiote existe chez l'individu asthmatique. Les probiotiques sont des micro-organismes qui peuvent réguler notre microbiome, conférant un effet bénéfique potentiel sur la santé. De ce fait, leur utilisation dans la prévention et la prise en charge de l'asthme est attractive et pourrait ouvrir de nouvelles perspectives thérapeutiques. En effet, les probiotiques sont très bien tolérés et présentent une grande sécurité d'emploi, tout en possédant des propriétés anti-inflammatoires et immunorégulatrices. Cet article permet de faire le point sur l'état actuel des connaissances quant à leur utilisation dans le cadre de l'asthme.

Inflammatory profile of induced sputum composition in systemic sclerosis and comparison with healthy volunteers.

Systemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared. In a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-ß, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%). The IS of SSc patients had a lower weight than HV (p<0.05, p<0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p < 0.0001), TGF-ß (p < 0.05), IL-8 (p < 0.05), YKL-40 (p < 0.0001) and MMP-7 (p < 0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p < 0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%) (r = = - 0.53, p < 0.01), FVC (%) (r = - 0.51, p < 0.01) and annualized ∆KCO (%) (r = 0.57, p < 0.05), between IS TGF-ß levels and annualized ∆FEV-1 (%) (r = = - 0.57, p < 0.05), between IS IGFBP-2 levels and annualized ∆KCO (%) (r = 0.56, p < 0.05). Our study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-ß, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-ß and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.

[Cystic lung diseases]. / Les maladies kystiques pulmonaires.

Cystic lung diseases present uncommonly and have an undetermined incidence. Cysts result from a broad spectrum of causative mechanisms and diseases leading to variable clinical presentations. The pathogenic mechanisms that can lead to lung cyst formation include infection, neoplastic, systemic, traumatic, genetic and congenital processes. A rigorous, systemic and multidisciplinary approach is advised in the diagnostic workup of these conditions. In this article, we review cystic lung diseases including their presentation and management.

[Idiopathic pulmonary fibrosis : from biomarkers to new therapeutic areas]. / La fibrose pulmonaire : des biomarqueurs à de nouveaux horizons thérapeutiques.

Pulmonary fibrosis is a pathological entity still too little understood today, burdened with significant morbidity and mortality. Idiopathic pulmonary fibrosis is a complex diagnostic disease requiring a multidisciplinary approach and in some cases the performance of a lung biopsy. In addition, the early identification of the pathology remains the key in order to preserve lung function as much as possible. In this context and in view of the diagnostic difficulty, it seems essential to identify new biomarkers to help with the differential diagnosis, the evaluation of the prognosis and the response to treatment. In addition, the evolution of the pathology remaining inexorable despite anti-fibrotic treatments, it appears critical to be able to identify new potential therapeutic routes.

La fibrose pulmonaire est une entité pathologique de nos jours encore trop méconnue, grevée d'une morbi-mortalité importante. La fibrose pulmonaire idiopathique est une maladie de diagnostic complexe nécessitant une approche pluridisciplinaire et, dans certains cas, la réalisation d'une biopsie pulmonaire. De plus, l'identification précoce de la pathologie reste la clé afin de préserver au maximum la fonction pulmonaire. Dans ce contexte et devant la difficulté diagnostique, il semble primordial de pouvoir identifier de nouveaux biomarqueurs permettant d'apporter une aide au diagnostic différentiel, à l'évaluation du pronostic et à la réponse au traitement. De plus, l'évolution de la pathologie restant inexorable en dépit de traitements anti-fibrotiques, il apparaît comme critique de pouvoir identifier de nouvelles voies thérapeutiques potentielles.

Sputum IL-25, IL-33 and TSLP, IL-23 and IL-36 in airway obstructive diseases. Reduced levels of IL-36 in eosinophilic phenotype.

INTRODUCTION: Alarmins ((IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)) are known to promote Th2 inflammation and could be associated with eosinophilic airway infiltration. They may also play a role in airway remodeling in chronic airway obstructive diseases such as asthma and chronic obstructive pulmonary disease (COPD). IL-23 and IL-36 were shown to mediate the neutrophilic airway inflammation as seen in chronic airway obstructive diseases. OBJECTIVES: The purpose of this project was to determine the expression and the production of these cytokines from induced sputum (IS) in patients with chronic airway obstructive diseases including asthmatics and COPD. The relationship of the mediators with sputum inflammatory cellular profile and the severity of airway obstruction was assessed. METHODS: The alarmins (IL-25, IL-33 and TSLP) as well as IL-23 and IL-36 concentrations were measured in IS from 24 asthmatics and 20 COPD patients compared to 25 healthy volunteers. The cytokines were assessed by ELISA in the IS supernatant and by RT-qPCR in the IS cells. RESULTS: At protein level, no difference was observed between controls and patients suffering from airway obstructive diseases regarding the different mediators. IL-36 protein level was negatively correlated with sputum eosinophil and appeared significantly decreased in patients with an eosinophilic airway inflammation compared to those with a neutrophilic profile and controls. At gene level, only IL-36, IL-23 and TSLP were measurable but none differed between controls and patients with airway obstructive diseases. IL-36 and IL-23 were significantly increased in patients with an neutrophilic inflammatory profile compared to those with an eosinophilic inflammation and were correlated with sputum neutrophil proportions. None of the mediators were linked to airway obstruction. CONCLUSIONS: The main finding of our study is that patients with eosinophilic airway inflammation exhibited a reduced IL-36 level which could make them more susceptible to airway infections as IL-36 is implicated in antimicrobial defense. This study showed also an implication of IL-36 and IL-23 in airway neutrophilic inflammation in chronic airway obstructive diseases.

[Chest radiological lesions in COVID-19 : from classical imaging to artificial intelligence]. / Les aspects radiologiques de la pneumopathie à COVID-19 : de l'imagerie conventionnelle à l'intelligence artificielle.

In the course of the pandemic induced by the appearance of a new coronavirus (SARS-CoV-2; COVID-19) causing acute respiratory distress syndrome (ARDS), we had to rethink the diagnostic approach for patients suffering from respiratory symptoms. Indeed, although the use of RT-PCR remains the keystone of the diagnosis, the delay in diagnosis as well as the overload of the microbiological platforms have led us to make almost systematic the use of thoracic imaging for taking in charge of patients. In this context, thoracic imaging has shown a major interest in diagnostic aid in order to better guide the management of patients admitted to hospital. The most common signs encountered are particularly well described in thoracic computed tomography. Typical imaging combines bilateral, predominantly peripheral and posterior, multi-lobar, ground glass opacities. Of note, it is common to identify significant lesions in asymptomatic patients, with imaging sometimes preceding the onset of symptoms. Beyond conventional chest imaging, many teams have developed new artificial intelligence tools to better help clinicians in decision-making.

Dans le décours de la pandémie induite par l'apparition d'un nouveau coronavirus (SARS-CoV-2; COVID-19) à l'origine d'un syndrome de détresse respiratoire aigu (SDRA), nous avons dû repenser l'approche diagnostique des patients souffrant de symptômes respiratoires. En effet, bien que l'usage de la RT-PCR reste la clé de voûte du diagnostic, le retard de diagnostic ainsi que la surcharge des plateformes microbiologiques nous ont menés à rendre quasi systématique l'usage de l'imagerie thoracique pour la prise en charge des patients. L'imagerie thoracique a démontré, dans ce contexte, un intérêt majeur dans l'aide au diagnostic afin d'orienter, au mieux, la prise en charge des patients admis à l'hôpital. Les signes les plus couramment rencontrés sont particulièrement bien décrits en tomodensitométrie thoracique. L'imagerie typique associe des lésions en verre dépoli bilatérales, multi-lobaires, à prédominance périphérique et postérieure. Il est classique d'identifier des lésions significatives chez des patients asymptomatiques, l'imagerie précédant parfois l'apparition de symptômes. Au-delà de l'imagerie thoracique conventionnelle, de nombreuses équipes ont développé de nouveaux outils d'intelligence artificielle afin d'aider, au mieux, les cliniciens dans la prise de décisions.

Could KL-6 levels in COVID-19 help to predict lung disease?

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. MATERIALS AND METHODS: Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. DISCUSSION AND CONCLUSION: Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary.

Single-center experience of patients with interstitial lung diseases during the early days of the COVID-19 pandemic.

INTRODUCTION: Patients with interstitial lung diseases (ILD) can be suspected to be at risk of experiencing a rapid flare-up due to COVID-19. However, no specific data are currently available for these patients. METHODS: We retrospectively analyzed a cohort of 401 patients with ILD and determined the proportion of patients hospitalized for proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific symptoms of COVID-19. RESULTS: We found that 1% of patients (n = 4) were hospitalized (1 in ICU) for COVID-19. In total, 310 of the 401 patients answered the phone call. Only 33 patients (0.08%) experienced specific symptoms of SARS-CoV-2 infection. CONCLUSION: Our study did not demonstrate any increased occurrence of severe COVID-19 in ILD patients compared to the global population. Based on our findings, we could not make any conclusion on the incidence rate of SARS-CoV-2 infection in patients with ILDs, or on the overall outcome of immunocompromised patients affected by COVID-19.

[Pulmonary arterial hypertension (PAH ) : a new era of pulmonary arterial vasodilatators]. / L'hypertension (artérielle) pulmonaire : l'apport des nouveaux vasodilatateurs artériels pulmonaires.

Pulmonary arterial hypertension (PAH) is a rare disease, characterized by a progressive increase in pulmonary arterial pressure. The therapeutic management of PAH patients has evolved significantly over the past decades following the appearance of new specific therapies, but also the performance of multiple clinical studies in an otherwise rare pathology. As a result, the care is very well codified and makes it possible to treat all patients at best. To date, we can cite four therapeutic families: endothelin receptor antagonists (ERA), drugs that interfere with the cyclic guanosine monophosphate (cGMP) pathway such as phosphodiesterase type 5 inhibitors (PDE5i) or the stimulator of soluble guanylate cyclase, prostacyclin analogues, and, finally, calcium antagonists. The therapeutic approach, formerly sequential, has proven to be insufficient in favor of an aggressive and rapidly progressive upfront therapeutic approach, making it possible to greatly improve the morbidity and mortality of patients. In this context, early management remains the most appropriate attitude and justifies recourse, from the first symptoms, to a competence center.

L'hypertension artérielle pulmonaire (HTAP) est une maladie rare, caractérisée par une majoration progressive de la pression artérielle pulmonaire. La prise en charge thérapeutique des patients en HTAP a fortement évolué dans les dernières décennies suite à l'apparition de nouvelles thérapeutiques spécifiques, mais également grâce à la réalisation de multiples études cliniques dans une pathologie par ailleurs rare. De ce fait, les prises en charge sont très bien codifiées et permettent de traiter, au mieux, l'ensemble des patients. A ce jour, nous pouvons citer quatre familles thérapeutiques : les antagonistes des récepteurs à l'endothéline (ERA), les médicaments interférant avec la voie de la guanosine monophosphate cyclique (GMPc) tels que les inhibiteurs de la phosphodiestérase de type 5 (PDE5i) ou le stimulateur de la guanylate cyclase soluble, les analogues aux prostacyclines, et, enfin, les antagonistes calciques. L'approche thérapeutique, anciennement séquentielle associant progressivement plusieurs thérapeutiques, s'est avérée insuffisante au profit d'une approche thérapeutique agressive et rapidement progressive, permettant d'améliorer fortement la morbi-mortalité des patients. Dans ce contexte, une prise en charge précoce reste l'attitude la plus appropriée et justifie un recours, dès les premiers symptômes, à un centre de compétence.

[Acute respiratory distress syndrome]. / Le syndrome de détresse respiratoire aiguë.

Since its first description in 1967, a lot of progress has been made in understanding the pathophysiology, diagnosis and management of acute respiratory distress syndrome (ARDS). This nosological entity is based on the appearance of a diffuse alveolar damage associating pulmonary epithelial barrier disruption with an alveolar filling, both responsible of profound hypoxemia and important morbi-mortality. Nowadays, ARDS remains a frequent syndrome, associated with various etiologies. Diagnosis is based on the occurrence of acute hypoxic respiratory failure not explained by cardiac insufficiency or volume overload, within 7 days after a recognized risk factor, and in the presence of bilateral pulmonary opacities not fully explained by effusions, atelectasis or nodules on the chest radiography. Survivors present an increased risk of developing cognitive decline, depression, post-traumatic stress, and typical ICU related side-effects such as polyneuropathy and sarcopenia. In this context and not withstanding significant recent progress in the field of mechanical ventilation and extra-corporeal respiratory assistance, early diagnosis remains essential to identify patients with ARDS in order to offer them the most appropriate therapy.

Depuis sa première description en 1967, des progrès majeurs ont été réalisés dans la compréhension de la physiopathologie, le diagnostic et la prise en charge du syndrome de détresse respiratoire aiguë (SDRA). Cette entité nosologique repose sur l'apparition d'un dommage alvéolaire diffus associant une rupture de la barrière épithéliale pulmonaire avec un comblement alvéolaire à l'origine d'une hypoxémie profonde. De nos jours, le SDRA reste un syndrome fréquent, grevé d'une mortalité élevée, et prenant source dans de multiples situations pathologiques. Le diagnostic du SDRA repose sur l'apparition d'une insuffisance respiratoire aiguë hypoxique non expliquée par une insuffisance cardiaque ou une surcharge volémique, dans un délai de 7 jours suivant l'apparition d'un facteur de risque reconnu, en présence d'opacités pulmonaires bilatérales non complètement expliquées par des épanchements, des atélectasies ou des nodules. Les survivants sont à haut risque de développer un déclin cognitif, une dépression, ou un stress post-traumatique en plus des effets secondaires classiques d'une longue hospitalisation en unité de soins intensifs que sont la polyneuropathie ou la sarcopénie. Dans ce contexte, et en dépit de progrès importants dans le domaine de la ventilation mécanique et de l'assistance respiratoire par circulation extra-corporelle, il reste primordial d'identifier précocement les patients souffrant de SDRA afin de leur proposer la thérapeutique la plus appropriée dès les premiers signes cliniques.

The human imperative of stabilizing global climate change at 1.5°C.

Increased concentrations of atmospheric greenhouse gases have led to a global mean surface temperature 1.0°C higher than during the pre-industrial period. We expand on the recent IPCC Special Report on global warming of 1.5°C and review the additional risks associated with higher levels of warming, each having major implications for multiple geographies, climates, and ecosystems. Limiting warming to 1.5°C rather than 2.0°C would be required to maintain substantial proportions of ecosystems and would have clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where the escalation of climate-related risks may prevent the achievement of the United Nations Sustainable Development Goals.

[Pulmonary arterial hypertension]. / L'hypertension artérielle pulmonaire.

Pulmonary arterial hypertension (PAH) is a rare vascular lung disease with a complex etiopathogeny characterized by an increased pulmonary arterial pressure of 25 mmHg or above assessed by right heart catheterization. The diagnosis is difficult due to the atypical presentation with shortness of breath requiring a sequential approach bringing at the end the clinician to perform a right heart catheterization. Nowadays, several therapies have proven to be efficient for treating PAH. Recently, international recommendations have moved to an initial combination therapy reducing the overall morbi-mortality of the patients. Therefore, early therapy appears to be a priority in PAH underlying the need for increasing the global knowledge around PAH.

L'hypertension artérielle pulmonaire (HTAP) est une maladie rare, rapidement évolutive et associée à une morbi-mortalité élevée. D'étiopathogénie pléomorphe, elle est définie par une majoration de la pression artérielle pulmonaire moyenne (PAPm) à une valeur supérieure ou égale à 25 mmHg, mesurée par cathétérisme cardiaque droit, sans majoration de la pression capillaire pulmonaire (PCP) ou pression artérielle pulmonaire occluse (PAPo), en l'absence de causes cardiaques et/ou respiratoires. Le diagnostic est rendu difficile par la présentation insidieuse et le caractère aspécifique des symptômes de la maladie. L'approche diagnostique est basée sur une suspicion échocardiographique et clinique, puis une approche séquentielle nécessitant, in fine, une mesure hémodynamique invasive. Au fil des dernières années, de nouvelles thérapeutiques ont été développées pour traiter l'HTAP. La stratégie actuelle recommande l'utilisation de combinaisons médicamenteuses dès que le diagnostic est établi. Dans ce contexte et au vu de l'impact significatif sur la morbi-mortalité des patients souffrant d'HTAP, il apparaît primordial d'instaurer au plus vite une thérapeutique spécifique dès la réalisation du diagnostic.

[Giant pulmonary artery aneurysms. Case report and proposal of management algorithm]. / Anévrysmes géants de l'artère pulmonaire : cas clinique et proposition d'un algorithme de diagnostic et de prise en charge.

Pulmonary artery aneurysm is a rare and multiform pathology related to multiple etiologies and therefore different pathophysiological mechanisms. Delineating homogenous sub-groups is a pre-requisite to refine medico-surgical management. The case of a giant PAA without pulmonary hypertension but associated to a dysplastic pulmonary valve is reported. This association could be in some instances the result of a congenital anomaly in the development of both the pulmonary valve and the root creating the conditions for further development of a pulmonary artery aneurysm. Whilst minor forms are usually asymptomatic, they can lead to lethal complications in huge sizes and are frequently associated via pulmonary valve insufficiency to right ventricular dysfunction. This specific association is discussed and a diagnostic algorithm for nosologic classification and management is proposed.

L'anévrysme de l'artère pulmonaire est une pathologie rare, qui répond à de multiples étiologies et autant de physiopathologies différentes. L'identification de sous-groupes constituant des entités cliniques homogènes est un prérequis pour préciser la prise en charge médico-chirurgicale optimale. Nous rapportons un cas d'anévrysme géant de l'artère pulmonaire principale, sans hypertension artérielle pulmonaire, mais associé à une dysplasie/dysfonction de la valve pulmonaire. Cette association pourrait être, dans certains cas, congénitale et liée à une anomalie de la morphogénèse de la valve et de la racine pulmonaire, association qui crée les conditions pour le développement d'un anévrysme. Asymptomatiques dans les formes mineures, les anévrysmes pulmonaires peuvent être causes de symptômes ou de complications gravissimes dans les formes très développées et entraînent souvent, par insuffisance pulmonaire, une dysfonction ventriculaire droite. Nous suggérons une classification claire de cette pathologie mal connue et, sur base de la littérature et de notre expérience personnelle, nous proposons un algorithme de prise en charge médico-chirurgicale.

[Pattern of biological changes in interstitial lung diseases]. / Comment j'explore Les modifications biologiques dans les pathologies infiltrantes pulmonaires.

Interstitial lung diseases (ILD) are a part of a vast and heterogeneous clinicopathological entity. The work-up have to rule out a granulomatosis or a secondary cause, before making the diagnosis of an idiopathic ILD. The etiological diagnosis is based on a multidisciplinary approach integrating a network of clinical and paraclinical datas. If the diagnosis remains unclear, a lung biopsy is suggested with a transbronchial approach (mainly cryobiopsy) or with a surgical approach (video-assisted thoracoscopy). This review article mainly describes the biological analyses that contribute to explore ILDs.

Les pathologies infiltrantes diffuses pulmonaires (PID) font partie d'une entité clinico-pathologique vaste et hétérogène. L'enjeu de la mise au point est d'exclure une granulomatose ou une étiologie secondaire, qu'elle soit de cause connue ou inconnue, avant de conclure à une PID idiopathique. Le diagnostic étiologique repose sur une approche multidisciplinaire intégrant un faisceau d'arguments issus de l'évaluation clinique et paraclinique. En cas de doute diagnostique, une biopsie pulmonaire est proposée par voie endotrachéale de type cryobiopsie ou par voie chirurgicale vidéo-assistée. Cette revue de littérature met principalement en exergue les éléments à rechercher d'un point de vue biologique chez un patient atteint d'une PID.

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.

[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.

[Acute respiratory distress revealing antisynthetase syndrome]. / Détresse respiratoire aiguë révélatrice d'un syndrome des antisynthétases.

Antisynthetase syndrome is a clinical entity characterized by specific anti-aminoacyl-tRNA-synthetase antibodies usually associated with inflammatory myopathy and interstitial lung disease. The classic presentation of the pathology is the pulmonary interstitium involvment, wich commonly determines the global prognosis. The subsequent diagnosis of antisynthetase syndrome in patients with acute respiratory distress syndrome (ARDS) is unusual, even more so when a veino-veinous (VV) extracorporeal membrane oxygenation (ECMO) is required. This article presents a clinical case of antisynthetase syndrome with severe ARDS successfully treated with immunosuppressive agents and ECMO.

Le syndrome des antisynthétases (SAS) est une pathologie multi-systémique auto-immune rare caractérisée par un trépied diagnostique associant la présence d'auto-anticorps anti-aminoacyl-ARNt synthétase, une myopathie inflammatoire et une pneumopathie interstitielle diffuse. L'atteinte pulmonaire parenchymateuse est la plus fréquemment rencontrée et détermine, de manière presque systématique, le pronostic global de la pathologie. L'identification d'un syndrome des antisynthétases dans le décours d'un syndrome de détresse respiratoire aigüe (SDRA) est rare, d'autant plus lorsque la mise en place d'un système d'oxygénation par membrane extracorporelle (ECMO) veino-veineuse (VV) est requise. Cet article présente un cas de SAS avec SDRA sévère, traité avec succès par immunosuppresseurs et ECMO.

[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.