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Background No large, prospective study has investigated respiratory symptoms in patients with inflammatory bowel diseases. We aimed to describe the prevalence of and factors associated with respiratory symptoms in patients with inflammatory bowel disease. Methods In an observational, prospective, cross-sectional study, we evaluated the frequency of respiratory symptoms using a validated self-reporting questionnaire from February 2019 to February 2021 during routine follow-up outpatient visits of patients with inflammatory bowel disease followed in the Gastroenterology Department of the Nancy University Hospital. In case of a positive questionnaire, patients were systematically offered a consultation with a pulmonologist in order to investigate a potential underlying respiratory disease. Results There were 325 patients included, and 180 patients had a positive questionnaire (144 with Crohn’s disease). Of the included patients, 165 (50.8%) presented with respiratory symptoms, with dyspnea being the most frequent symptom (102 patients). There were 102 patients (56.7%) who benefited from a consultation in the pulmonology department: 43 (42.2%) were diagnosed with a respiratory disease, mainly asthma (n = 13) or chronic obstructive pulmonary disease (n = 10). Fourteen patients (13.7%) had obstructive sleep apnea. A body mass index increase, being a smoker or ex-smoker, and having articular extra-intestinal manifestations were independently associated with a higher prevalence of respiratory symptoms. Conclusions Half of patients with inflammatory bowel disease reported respiratory symptoms in our study. Patients with inflammatory bowel disease should be systematically screened, as pulmonary disease is frequently present in this population, with specific attention being given to smokers or ex-smokers and patients with extra-articular intestinal manifestations.

Among interstitial pneumonia with autoimmune features (IPAF) patients, identifying those at risk to develop a connective tissue disease (CTD) during the disease course is a key issue. The aim of this study was to evaluate the incidence of definite CTD diagnosis in IPAF patients during follow-up.We performed a multicentric cohort study of interstitial lung disease (ILD) from 2010 to 2017 in pneumology and immunology departments of tertiary care centers. Patients with a known cause of ILD (including established CTD) at diagnosis were excluded. Among patients with idiopathic ILD and at least three years of follow-up, two groups (IPAF and non-IPAF) were retrospectively analyzed at time of diagnosis.A total of 249 patients with ILD were enrolled, including 70 IPAF and 179 non-IPAF patients. After a mean follow-up time of 77 ± 44 months, 18/70 IPAF patients (26%) had a CTD diagnosis - 9 antisynthetase syndrome, 8 systemic sclerosis and 1 overlap myositis - compared with 4/179 non-IPAF patients (2%). IPAF patients were at higher risk of CTD occurrence at 3 years of follow-up compared to non-IPAF patients (HR 10.1, 95% CI 3.1-33.1, p 0. 01). IPAF patients progressing to CTD tended to be younger, more often female and have more frequently puffy fingers, capillaroscopy abnormalities and antisynthetase antibodies at diagnosis.We found that a significant proportion of IPAF patients had associated CTD diagnosis during follow-up. Prospective studies are needed to confirm baseline predictive factors of CTD occurrence in IPAF patients.

BackgroundSurvivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life.MethodsAdults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study.ResultsAmong 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide (DLCO) and significant radiological sequelae, respectively. During extended follow-up, bothDLCOand forced vital capacity percentage predicted increased by means of +4 points at 6 months and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated withDLCOat 3 months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images.ConclusionsAlthough pulmonary function and radiological abnormalities improved up to 1 year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

Resume Introduction Le trouble depressif est une comorbidite frequente au cours de la broncho-pneumopathie chronique obstructive (BPCO) et retentit negativement sur la qualite de vie. Cette etude a pour but d’evaluer l’impact du reentrainement a l’exercice (RE) sur les symptomes cliniquement significatifs de depression. Methodes Parmi les 515 patients atteints de BPCO inclus dans un programme de RE a domicile, la qualite de vie (questionnaire de Saint-George : SGRQ), les symptomes de depression (score de Beck version courte [BDI-SF]), et le temps d’endurance (TE) ont ete mesures a l’inclusion (T0) et a 12 mois (T12) chez 182 patients (deces n = 10 ; abandons n = 84 ; donnees manquantes n = 239). Ce RE comportait des seances initiales hospitalieres, puis a domicile encadrees periodiquement par un professionnel de sante. Resultats Le BDI-SF etait de 4,2 ± 5,1 et 2,7 ± 4,3 (p Conclusion Le RE ameliore les symptomes cliniquement significatifs de depression au cours de la BPCO. Ces resultats sont correles a l’amelioration du test d’endurance.

Resume Introduction L’atteinte respiratoire liee a la maladie associee aux IgG4, proteiforme et d’intensite variable, peut etre grave. Nous rapportons un cas de maladie associee aux IgG4 revelee par une pneumopathie infiltrante diffuse d’aggravation rapidement progressive. Observation Il s’agit d’un homme âge de 69 ans, ancien fumeur, hospitalise initialement pour enquete etiologique d’une pneumopathie interstitielle diffuse revelee par une toux, une dyspnee febrile et une alteration de l’etat general evoluant depuis 3 mois. L’aggravation rapide de l’hypoxemie imposait un transfert en soins intensifs respiratoires pour instauration d’une ventilation non invasive (VNI) et d’une oxygenotherapie a haut debit. Le scanner thoracique revelait des condensations lobaires inferieure droite et moyenne, des plages de verre depoli diffuses, un epaississement des septa inter-lobulaires ainsi que des adenomegalies mediastinales et une pleuresie bilaterale de faible abondance. Une maladie associee aux IgG4 etait suspectee devant une augmentation des IgG4 seriques. La confirmation diagnostique fut obtenue par une biopsie renale montrant une glomerulonephrite aigue avec une infiltration lympho-plasmocytaire, une fibrose d’aspect storiforme et plus de 60 plasmocytes IgG4+ par champ a fort grossissement. L’evolution etait rapidement favorable sous corticotherapie systemique. Conclusion Habituellement au second plan, l’atteinte respiratoire de la maladie associee aux IgG4 peut egalement se reveler par une insuffisance respiratoire severe avec ou sans atteinte extra-thoracique.

International audience; No abstract available

BackgroundDrugs approved for the treatment of pulmonary arterial hypertension (PAH) improve long-term outcomes. These drugs have pulmonary vasodilator properties which may potentially cause a decrease in arterial oxyhaemoglobin saturation (SaO2) in some patients. The present retrospective study of the French Pulmonary Hypertension Registry aimed to describe the clinical characteristics and outcomes of patients showing a ≥3% decrease inSaO2while treated with PAH drugs.MethodsWe reviewed 719 PAH patients. The exclusion criteria were PAH associated with congenital heart disease and PAH with overt features of venous/capillaries involvement.Results173 (24%) patients had a ≥3% decrease inSaO2. At diagnosis, they were older with a lower diffusing capacity of the lung for carbon monoxide and a shorter 6-min walk distance compared with those who did not display a ≥3% decrease inSaO2. The percentage of patients meeting the European Society of Cardiology/European Respiratory Society (ESC/ERS) low-risk criteria at re-evaluation was significantly lower in those with a ≥3% decrease inSaO2and more patients started long-term oxygen therapy in this group (16%versus5%; pSaO2was associated with a poorer survival (hazard ratio 1.81, 95% CI 1.43–2.34; pSaO2was a prognostic factor independent of age at diagnosis and ESC/ERS risk stratification at follow-up.ConclusionsWhen treated with PAH drugs, a large subset of patients experience a ≥3% decrease inSaO2, which is associated with worse long-term outcomes and reduced survival.

Home respiratory equipment (HRE) designed for the management of chronic respiratory failure includes oxygen therapy (OThe French open access national health insurance aggregated data was used to estimate the evolution of theses parameters from 2006 to 2019.The number of patients treated by HRE increased by 117% between 2006 and 2019, reaching a total of 245,896 patients (367/100,000). Prescriptions for OOur results highlighted the high rate of HRE prescription, but with cost control as a result of adapted health policies.

Viral respiratory infections, including SARS-CoV-2 infection, can trigger respiratory symptoms among patients suffering from chronic respiratory diseases, leading to exacerbations and hospitalizations. Despite the tropism of SARS-CoV-2 into the respiratory tract, chronic respiratory diseases do not seem to be risk factors for severe forms of COVID-19.To assess whether hospitalized patients for COVID-19 with chronic respiratory diseases were at lower risk of developing a severe form than other patients.This French study included patients admitted to hospital in COVID-19 ward, suffering from a SARS-CoV-2 infection, diagnosed on RT-PCR or chest computed tomography associated with clinical symptoms, from March 15 to June 30, 2020. Ambulatory patients who were tested in the emergency department and patients with severe hypoxaemia requiring intensive care were not included. All data were collected from electronic medical records up to discharge of the patient.617 patients were included: 125 with a chronic respiratory disease, mainly chronic obstructive pulmonary disease (45%) and asthma (30%). The percentage of patients scoring 6 or higher on the WHO Clinical Progression Scale during hospital stay was lower in patients with chronic respiratory disease compared to those without chronic respiratory disease (21.6% versus 31.3%, respectively, p = 0.03). Among patients with chronic respiratory disease, temperature above 38 °C on admission (OR 16.88 (95% CI 4.01-71.00)), lymphopenia (OR 5.08 (1.25-20.72)), CPAP therapy (OR 4.46 (1.04-19.17)) and age (OR 1.09 (1.02-1.16)) were associated with an increased risk to reach a score of 6 or above.Hospital admissions in COVID-19 ward of patients suffering from chronic respiratory diseases are at lower risk of developing a severe form of COVID- 19, especially in patients with chronic obstructive pulmonary disease or asthma. Prospective studies would confirm our results and allow to better organize the follow-up of these patients in a pandemic period.

Study Objectives:Our objectives were to determine in an obese population (body mass index > 35 kg/m2) the number of patients, after gastric bypass (GBP), who no longer met French Ministry of Health...

International audience

Introduction: Alveolar type 2 cells (AT2) play a key role in alveolar regeneration after alveolar damage. Mechanisms involved in this process are not well known. Aims and Objectives: Targeting p16INK4a, a cell cycle inhibitor, in AT2 could be a way to promote alveolar regeneration. Methods: In vitro alveolar organoids were obtained by co-culturing EpCAM+ cells (sorted with magnetic beads from lungs of p16INK4a-/- or wild type (WT) mice) with WT lung primary fibroblasts. Colony forming units (CFU), organoid size, organoid types (alveolar, bronchoalveolar by pro-SpC and ACT staining) were quantified at D14 and D21. Organoids from emphysematous mice (elastase model) were compared to organoids from PBS-injected mice as a control with the same genetic background (p16INK4a-/- or WT). In vivo, morphological analysis (mean linear intercept) and AT2 number were quantified in elastase or PBS injected mice at D21 and D90 to assess alveolar destruction and regeneration according to WT or p16INK4a-/- genotype. Results: Organoids made with p16INK4a-/- EpCAM+ cells were as numerous but had an increased size compared to those made from WT EpCAM+ cells at D14 and D21. CFU and organoid size from emphysematous mice were significantly decreased compared to control mice. Number and size of organoids made with p16INK4a-/- EpCAM+cells from emphysematous mice were higher than organoids made with WT EpCAM + cells from emphysematous mice. In vivo, p16INK4a deletion was associated with an increase of AT2 at D21 without a protective effect on alveolar architecture. At D90, p16INK4a-/- mice had less emphysema than WT mice. Conclusions: p16INK4a deletion increases endogenous alveolar regeneration by AT2 cells. Mechanisms involved remain to be determined.

Introduction L’objectif de ce travail etait de determiner si les donnees morphologiques des voies aeriennes proximales de 3e et 4e generation issues du scanner thoracique realise dans le cadre des soins courants permettent de predire le phenotype « exacerbateur frequent » chez des patients atteints de BPCO. Methodes Les patients BPCO suivis au CHU de Nancy qui avaient eu un scanner thoracique dans le cadre des soins courants ont ete inclus dans l’analyse. Les donnees cliniques et fonctionnelles ont ete recueillies de facon retrospective. Le nombre d’exacerbations a ete recense au cours de l’annee precedant le scanner et l’annee suivante. Le phenotype « exacerbateur frequent » etait defini par au moins 2 exacerbations ou une hospitalisation au cours d’une annee. Les dimensions des voies aeriennes proximales de 3e et 4e generation ont ete obtenues de facon quantitative avec le calcul de la surface de la lumiere (LA) et de la paroi (WA) bronchique, le pourcentage de la surface de la paroi par rapport a la surface totale de la bronche (WAP) et l’epaisseur de la paroi bronchique (WT). Resultats Les scanners de 69 patients BPCO ont ete analyses. Il n’y avait pas de relation entre d’une part l’âge, le sexe, l’IMC, la severite de l’obstruction bronchique en regard du VEMS (% de la valeur predite), l’hematose et d’autre part, les donnees morphologiques des bronches de 3e et 4e generation. Lorsque le phenotype « exacerbateur frequent » etait defini au cours de l’annee precedant le scanner, aucun des parametres morphologiques n’etait associe au risque de survenue d’exacerbations. En revanche une augmentation de la surface de la paroi bronchique de 3e generation au-dessus de la mediane etait un facteur independant du phenotype « exacerbateur frequent » dans l’annee qui suivait la realisation du scanner (OR 1,1; IC95: 1,02–1,18; p = 0,013) et il existait une correlation positive entre d’une part la surface, l’epaisseur de la paroi bronchique et d’autre part le nombre d’exacerbations. Les coefficients de correlations etaient respectivement: 0,259 (WA3); 0,290 (WA4); 0,239 (WT3). Conclusion Seule la surface de la paroi bronchique de 3e generation etait associee au phenotype « exacerbateur frequent » dans l’annee suivant le scanner thoracique. L’identification de phenotypes morphologiques de BPCO issus du scanner thoracique, pourrait permettre de mieux predire le risque de survenue d’exacerbations et la progression de la maladie.

The objectives of this study were to describe the prevalence and characteristics of radiographic lesions of the hands, and calcifications of the spine on computer tomography scans (CT-scans), and to investigate the relationships between radiographic and CT-scan abnormalities and clinical features in a population of patients with systemic sclerosis (SSc). Subjects underwent X-ray examination of the hands, and thoracic or thoraco-abdominal and pelvic CT scan or lumbar CT scan in the year. Structural lesions on hand X ray was scored and spinal calcifications were evaluated in the anterior, intracanal and posterior segments. Intra and inter-reliability was tested for radiography and CT- scan. Prognostic factors considered were interstitial pulmonary lesions on the CT scan, pulmonary arterial hypertension (PAH) and death. This study involved 77 SSc patients, 58 (75%) with limited cutaneous SSc (lcSSc) and 19 (25%) with diffuse SSc (dSSc). The prevalences of radiographic lesions of the hand were 28.6% for periarticular calcifications and 26% for calcinosis. On CT scan, 64 (83%) patients exhibited at least 1 calcification. Spine calcifications were depicted in 80.5%, 27.3%, and 35.1% at the anterior, intracanal and posterior segments respectively. Calcifications were mainly localized on thoracic spine. Inter reader reliabilities were good for hands and moderate for spine respectively. Spine calcifications and periarticular calcifications in the hands were associated (P = .012). Calcinosis in the hands was related to PAH (P = .02). Posterior calcification segment and foraminal calcifications were associated with interstitial lung disease (ILD) (P = .029) and death (P = .001). More than 80% of systemic sclerosis patients presented spine calcifications. A significant association between hands and spinal calcifications were confirmed and some localization in the posterior segment considered as a bad prognostic factor.

Resume Introduction Les pneumopathies a eosinophiles sont caracterisees par une alveolite a polynucleaires eosinophiles. Elles peuvent etre idiopathiques ou relever de differentes causes. L’origine medicamenteuse doit etre toujours evoquee. Observation Nous rapportons le cas d’une femme de 57 ans, fumeuse, atteinte d’un trouble bipolaire, traitee par divalproate de sodium depuis plus de 2 ans, qui presentait une dyspnee non febrile depuis 5 mois. Les explorations realisees montraient une hypoxemie severe, un trouble ventilatoire obstructif severe, de multiples images en verre depoli avec un aspect de crazy paving au scanner thoracique, une hypereosinophilie sanguine et une alveolite a eosinophiles au lavage broncho-alveolaire. Le diagnostic de pneumopathie a eosinophiles au divalproate de sodium etait retenu apres un bilan etiologique exhaustif, et l’amelioration radio-clinique etait rapide apres l’arret du medicament, sans recours a la corticotherapie systemique. Conclusion Le divalproate de sodium peut induire une pneumopathie a eosinophiles plusieurs annees apres son introduction. Un diagnostic rapide et un arret du traitement ont permis une guerison complete dans le cas rapporte.

Background: Assessment of prognosis is of major importance when deciding on a therapeutic strategy in patients with pulmonary arterial hypertension (PAH). Objectives: The aim of this study was to investigate the prognostic value of pulmonary hemodynamics during exercise and changes during treatment in patients with PAH. Methods: Consecutive incident patients (n = 49) with PAH undergoing right heart catheterization at rest and during a constant workload cycle exercise in supine position were included. Predictors of survival were identified at baseline using Cox proportional hazard regression models in a univariate analysis unadjusted and adjusted for age and gender. Results: During a median follow-up period of 42 months, 13 (27%) of the 49 patients studied died. Two predictors of death were found: rest-to-exercise changes in heart rate and systolic pulmonary artery pressure. Adjusted hazard ratios were 0.92 (95% CI 0.86–0.99) and 0.93 (95% CI 0.88–0.99), respectively. These 2 variables were correlated with each other (r = 0.55, p < 0.001). Conclusions: Rest-to-exercise changes in heart rate and systolic pulmonary artery pressure measured at diagnosis are predictors of survival in patients with PAH. These measurements taken from an exercise test reflect right ventricular function.

International audience; Rationale: Promoting endogenous pulmonary regeneration is crucial after damage to restore normal lungs and prevent the onset of chronic adult lung diseases.Objectives: To investigate whether the cell-cycle inhibitor p16INK4a limits lung regeneration after newborn bronchopulmonary dysplasia (BPD), a condition characterized by the arrest of alveolar development, leading to adult sequelae.Methods: We exposed p16INK4a-/- and p16INK4a ATTAC (apoptosis through targeted activation of caspase 8) transgenic mice to postnatal hyperoxia, followed by pneumonectomy of the p16INK4a-/- mice. We measured p16INK4a in blood mononuclear cells of preterm newborns, 7- to 15-year-old survivors of BPD, and the lungs of patients with BPD.Measurements and Main Results: p16INK4a concentrations increased in lung fibroblasts after hyperoxia-induced BPD in mice and persisted into adulthood. p16INK4a deficiency did not protect against hyperoxic lesions in newborn pups but promoted restoration of the lung architecture by adulthood. Curative clearance of p16INK4a-positive cells once hyperoxic lung lesions were established restored normal lungs by adulthood. p16INK4a deficiency increased neutral lipid synthesis and promoted lipofibroblast and alveolar type 2 (AT2) cell development within the stem-cell niche. Besides, lipofibroblasts support self-renewal of AT2 cells into alveolospheres. Induction with a PPARγ (peroxisome proliferator-activated receptor γ) agonist after hyperoxia also increased lipofibroblast and AT2 cell numbers and restored alveolar architecture in hyperoxia-exposed mice. After pneumonectomy, p16INK4a deficiency again led to an increase in lipofibroblast and AT2 cell numbers in the contralateral lung. Finally, we observed p16INK4a mRNA overexpression in the blood and lungs of preterm newborns, which persisted in the blood of older survivors of BPD.Conclusions: These data demonstrate the potential of targeting p16INK4a and promoting lipofibroblast development to stimulate alveolar regeneration from childhood to adulthood.

Resume Introduction Les anticorps anti programmed death-1 (PD-1) et programmed death-ligand 1 (PD-L1) sont des immunotherapies utilisees dans le traitement de nombreuses tumeurs solides. Des cas de pneumopathies interstitielles induites par les anti PD-1 ont largement ete decrits, mais les donnees sont moins nombreuses avec les anti PD-L1. L’avelumab est une nouvelle immunotherapie de la classe des anti PD-L1. Observation Il s’agit d’une femme de 66 ans, tabagique sevree, traitee par avelumab et axitinib depuis le 15 novembre 2016 pour un cancer renal a cellules claires. Elle presente une pneumopathie interstitielle decouverte fortuitement 4 mois apres le debut du traitement avec des lesions scannographiques de verre depoli, des reticulations intra-lobulaires et une adenopathie de la zone 4R. Le bilan exhaustif ne met pas en evidence de retentissement fonctionnel respiratoire, ni d’etiologie infectieuse ou immunologique. Les anomalies radiologiques regressent spontanement apres l’arret du traitement, permettant de retenir le diagnostic de pneumopathie medicamenteuse. Conclusion L’avelumab peut induire une pneumopathie interstitielle. Son mecanisme incertain necessite des etudes complementaires. Une surveillance des explorations fonctionnelles respiratoire et du scanner thoracique est necessaire pour une prise en charge precoce.

The analysis of right ventriculo-arterial coupling (RVAC) from pressure-volume loops is not routinely performed. RVAC may be approached by the combination of right heart catheterization (RHC) pressure data and cardiac magnetic resonance (CMR)-derived right ventricular (RV) volumetric data. RV pressure and volume measurements by Doppler and three-dimensional echocardiography (3DE) allows another way to approach RVAC.Ninety patients suspected of having pulmonary hypertension underwent RHC, 3DE, and CMR (RHC mean pulmonary artery pressure [mPAP] 37.9 ± 11.3 mm Hg; range, 15-66 mm Hg). Three-dimensional (3D) echocardiography was performed in 30 normal patients (echocardiographic mPAP 18.4 ± 3.1 mm Hg). Pulmonary artery (PA) effective elastance (Ea), RV maximal end-systolic elastance (Emax), and RVAC (PA Ea/RV Emax) were calculated from RHC combined with CMR and from 3DE using simplified formulas including mPAP, stroke volume, and end-systolic volume.Three-dimensional echocardiographic and RHC-CMR measures for PA Ea (3DE, 1.27 ± 0.94; RHC-CMR, 0.71 ± 0.52; r = 0.806, P .001), RV Emax (3DE, 0.72 ± 0.37; RHC-CMR, 0.38 ± 0.19; r = 0.798, P .001), and RVAC (3DE, 2.01 ± 1.28; RHC-CMR, 2.32 ± 1.77; r = 0.826, P .001) were well correlated despite a systematic overestimation of 3DE elastance parameters. Among the whole population, 3D echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D echocardiographic RV Emax were significantly lower in patients with mPAP25 mm Hg (n = 41) than in others (n = 79). Among the 90 patients who underwent RHC, 3D echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D echocardiographic RV Emax increased significantly with increasing levels of pulmonary vascular resistance.Three-dimensional echocardiography-derived PA Ea, RV Emax, and RVAC correlated well with the reference RHC-CMR measurements. Ea and RVAC but not Emax were significantly different between patients with different levels of afterload, suggesting failure of the right ventricle to maintain coupling in severe pulmonary hypertension.

Resume Introduction L’hypertension arterielle pulmonaire (HTAP) est une maladie vasculaire pulmonaire dont le pronostic est sombre. Le traitement par analogues des prostacyclines i.v. continu impose la mise en place d’un catheter tunnelise. Le taux d’infection liee au catheter tunnelise dans ce contexte est peu frequent du fait du pH alcalin des solutions d’analogues des prostacyclines. Observation Une patiente de 50 ans, atteinte d’HTAP heritable traitee par bosentan, sildenafil et epoprostenol presentait une alteration de l’etat general avec un amaigrissement de 9 kg sur une periode de 12 mois, sans syndrome infectieux ou tumoral. On ne notait pas d’aggravation hemodynamique. Le diagnostic est pose a un an de suivi, la patiente presentant une febricule a 38°C et un syndrome inflammatoire biologique. Les hemocultures peripheriques repetees reviennent positives a Dietzia, un bacille coryneforme alcalophile. L’evolution est favorable sous antibiotherapie. Conclusion L’infection de catheter tunnelise doit etre evoquee en cas d’aggravation clinique ou hemodynamique chez un patient atteint d’HTAP traite par analogues des prostacyclines administres en intraveineux. Dans ce contexte, le laboratoire doit etre prevenu de la recherche de germes a croissance lente.

Background Pulmonary arterial hypertension (PAH) is a rare complication of systemic lupus erythematosus (SLE). Methods We identified all patients with SLE and PAH (SLE-PAH) who were enrolled in the French Pulmonary Hypertension Registry with a diagnosis confirmed by right heart catheterization (RHC). A control group of 101 patients with SLE without known PAH was selected from SLE expert centers participating in the Pulmonary Hypertension Registry. Survival was estimated by the Kaplan-Meier method. Hazard ratios associated with potential predictors of death were estimated using Cox proportional hazard models. Results Of the 69 patients with SLE-PAH identified in the French Pulmonary Hypertension Registry, 51 were included in the study. They did not differ from the control group regarding age, sex, or duration of SLE at the time of the analysis but had a higher frequency of anti-SSA and anti-SSB antibodies. The delay between SLE diagnosis and PAH diagnosis was 4.9 years (range, 2.8-12.9) years. The 3- and 5-year overall survival rates were 89.4% (95% CI, 76.2%-96.5%) and 83.9% (95% CI, 68.8%-92.1%), respectively. The survival rate was significantly better in patients with anti-U1-RNP antibodies ( P = .04). Conclusions Patients with SLE-PAH have an overall 5-year survival rate of 83.9% after the PAH diagnosis. Anti-SSA/SSB antibodies may be a risk factor for PAH, and the presence of anti-U1-RNP antibodies appears to be a protective factor regarding survival.

Introduction Les pneumocytes de type 2 (p2) jouent un role cle dans les processus de regeneration apres des dommages alveolaires. Les mecanismes sous-jacents sont peu connus. L’objectif de ce travail est d’examiner si l’inhibiteur du cycle cellulaire p16INK4a module des proprietes des p2 et augmentant leurs capacites a induire une regeneration alveolaire. Methodes Des organoides pulmonaires ont ete realises par la mise en co-culture de cellules EpCAM+ obtenues par tri cellulaire magnetique (CD31-, CD45-, CD16/32-, CD90-, CD271-, Ter119-, EpCAM+) a partir de poumon de souris p16INK4a-/− ou WT avec des fibroblastes primaires pulmonaires WT. Une analyse de la taille et du nombre de colonies d’organoides formees (colony forming unit : CFU) et du type d’organoides (alveolaires ou bronchiques avec les marquages proSpC et acetylated tubulin-ACT) a ete realisee a 14 et 21 jours de culture. Dans un deuxieme temps, ces organoides ont ete obtenus a partir de poumon de souris emphysemateuses (J21 apres instillation d’elastase 2UI) compare a des souris controles (serum physiologique), p16INK4a-/− ou WT. Des analyses morphometriques (mean linear intercept) et le nombre de p2 ont ete realises 21 et 90 jours apres elastase. Resultats Les organoides formes de cellule EpCAM- p16INK4a-/− avaient une taille plus importante que ceux forme a partir d’EpCAM-WT a J14 (p = 0,046) et J21 (p = 0,0001). La majorite des organoides etaient alveolaires. La taille des organoides issus de souris emphysemateuses etait plus basse par rapport aux controles (p = 0,019), avec une tendance a la diminution du nombre de CFU. Les organoides issus de souris emphysemateuses p16INK4a-/− etaient de taille plus importante et plus nombreux que ceux issus de souris emphysemateuses WT. In vivo, la deletion de p16 etait associee 21 jours apres instillation d’elastase a un nombre plus important de p2 dans le poumon sans impact sur l’emphyseme. 90 jours apres elastase, les souris p16INK4a-/− avaient moins d’emphyseme (mean linear intercept) que les souris WT. Conclusions Inhiber p16INK4a augmente les capacites de regeneration endogene alveolaire des p2. Les mecanismes impliques restent a determiner.

Introduction Les traitements specifiques de l’hypertension arterielle pulmonaire (HTAP) se sont averes efficaces dans de nombreux essais randomises controles. Cependant, en raison de l’effet vasodilatateur pulmonaire de ces traitements, ils peuvent potentiellement entrainer une diminution de la saturation arterielle en oxygene (SaO2) [1] . L’objectif de l’etude etait de determiner si un pourcentage significatif de patients presentait une diminution de la SaO2 de 3 % ou plus sous l’effet des traitements specifiques de l’HTAP et si ces patients presentaient des caracteristiques distinctives. Methodes Dans une etude retrospective, nous avons inclus 719 patients atteints d’HTAP inscrits au registre francais, entre 2008 et 2019. Les criteres d’inclusion etaient d’avoir eu un diagnostic d’HTAP, une re-evaluation dans les douze mois suivant le diagnostic, avoir recu au moins un traitement specifique entre le diagnostic et la re-evaluation et avoir eu un catheterisme cardiaque droit ainsi que des gaz du sang arteriels en air ambiant aux deux visites. Les criteres d’exclusion etaient l’HTAP associee a une cardiopathie congenitale et l’HTAP presentant des caracteristiques de maladie veino-occlusive pulmonaire et/ou d’hemangiomatose capillaire pulmonaire. La SaO2 n’etant pas disponible dans les donnees du registre francais, elle a ete calculee a l’aide de l’equation de Severinghaus. Resultats Cent soixante-treize (24 %) patients ont eu une diminution de 3 % ou plus de la SaO2 ( Tableau 1 ). Ces patients etaient plus âges au moment du diagnostic (64 ± 12 vs 58 ± 15, p Conclusion Un nombre relativement important de patients atteints d’HTAP ont connu une diminution significative de la SaO2 sous traitement specifique. La mesure de la SaO2 au diagnostic et lors de la re-evaluation, en air ambiant et au repos, pourrait etre un outil non invasif de re-evaluation des patients atteints d’HTAP.

4-Aminopyridine (4-AP) is a recent treatment indicated to improve walking in patient with multiple sclerosis. We report the first case of pulmonary arterial hypertension (PAH) that we attribute to the use of 4-AP. A 64-year-old woman with multiple sclerosis presented with dyspnea. After excluding other secondary causes of pulmonary hypertension, a diagnosis of severe PAH due to 4-AP was made based on right heart catheterization. History revealed that the dyspnea began with the initiation of 4-AP. After discontinuation of 4-AP therapy and initiation of ambrisentan and tadalafil, dyspnea and pulmonary arterial pressure have improved significantly and one specific PAH treatment was stopped. 4-AP is an outward rectifying potassium channel blocker with a vasoconstrictor effect in animal's pulmonary artery. According to the chronological sequence of events, the lack of other etiology, and its pharmacological plausibility, 4-AP is highly suspected to have induced our patient's PAH.

Introduction: Lung regeneration is essential for damage recovering after lung injury at different age of life. Whether lipofibroblasts (LIF) are able to enhance endogenous alveolar regeneration once alveoli are damaged remains to be determined. Aim: To determine in a mouse model of bronchopulmonary dysplasia if a lipid switch of fibroblasts to LIF induce a curative lung regeneration. Methods: Wt C57BL/6J mice were exposed to hyperoxia (85% O2) or room air from days 3 to 14 of post-natal life. Rosiglitazone (RGZ), a PPARγ agonist which activates fibroblasts differentiation into LIF, was administered intraperitoneally at a dose of 5µg/g of mice daily, 5 days a week, starting after hyperoxia exposure, until adulthood (D60). Tissues were immunostained with anti-ADRP and anti-proSpC antibodies for LIF and AT2 detection respectively. Number of alveoli were estimated by the mean linear intercept and secondary septation by septal crest number (Weigert). Results: Compared to mice exposed to room air, mice exposed to hyperoxia presented a significant decreased number of LIF in lung associated with an arrested alveolar development revealed by a reduced number of alveoli and a concomitant disruption of secondary septation. Compared to hyperoxic, non-treated mice, RGZ administration increased the number of LIF and AT2 cells in the lung, associated with an increase in the number of alveoli and septal crests at adulthood. Conclusion: Switching fibroblasts towards LIF through PPARγ agonist administration induces lung regeneration after hypoalveolization due to post-natal hyperoxia. Administration of PPARγ agonists can be a new pharmacologic strategy to promote lung recovery after injury.

Background Breathlessness is the prominent symptom of chronic obstructive pulmonary disease (COPD). Despite optimal therapeutic management including pharmacological and non-pharmacological interventions, many COPD patients exhibit significant breathlessness. Chronic breathlessness is defined as breathlessness that persists despite optimal treatment of the underlying disease. Because of the major disability related to chronic breathlessness, symptomatic treatments including opioids have been recommended by several authors. The prevalence of chronic breathlessness in COPD and its management in routine clinical practice have been poorly investigated. Our aim was to examine prevalence, associated characteristics and management of chronic breathlessness in patients with COPD recruited in a real-life tertiary hospital-based cohort. Methods A prospective study was conducted among 120 consecutive COPD patients recruited, in stable condition, at Nancy University Hospital, France. In parallel, 88 pulmonologists of the same geographical region were asked to respond to an on-line questionnaire on breathlessness management. Results Sixty four (53%) patients had severe breathlessness (modified Medical Research Council scale≥3), despite optimal inhaled medications for 94% of them; 40% had undergone pulmonary rehabilitation within the past 2 years. The severity of breathlessness increased with increasing airflow limitation. Breathlessness was associated with increased symptoms of anxiety, depression and with osteoporosis. No relation was found with other symptoms, exacerbation rate, or cardiovascular comorbidities. Among the patients with chronic breathlessness and Hospitalized Anxiety and/or Depression score > 10, only 25% were treated with antidepressant or anxiolytic. Among the pulmonologists 46 (52%) answered to the questionnaire and expressed a high willingness to prescribe opioids forchronic breathlessness, which contrasted with the finding that none of these patients received such treatments against breathlessness. Conclusion Treatment approaches to breathlessness and associated psychological distress are insufficient in COPD. This study highlights underuse of pulmonary rehabilitation and symptomatic treatment for breathlessness. Electronic supplementary material The online version of this article (10.1186/s12890-019-0851-5) contains supplementary material, which is available to authorized users.

Resume Introduction L’histoire naturelle des maladies pulmonaires orphelines est rarement connue. Nous presentons l’evolution a long terme d’une forme bronchectasiante de la maladie a depots de chaines legeres (MDCL) d’immunoglobulines non amyloides. Observation Il s’agit d’une femme fumeuse chez qui le diagnostic de dilatation des bronches d’etiologie indeterminee est porte a l’âge de 50 ans. Dix ans apres, l’hypothese d’une MDCL pulmonaire est evoquee devant l’aspect caracteristique des bronchectasies, l’apparition de kyste pulmonaires, l’augmentation du taux serique des chaines legeres Kappa. La confirmation diagnostique est obtenue par biopsie pulmonaire chirurgicale. Aucune hemopathie maligne n’est retrouvee. Durant les 12 ans de suivi, l’aggravation de la dyspnee d’effort est lente et concomitante a l’extension des bronchectasies et des kystes realisant un aspect de pneumopathie multikystique. Les EFR montrent une preservation des volumes pulmonaires et une diminution moderee de la capacite de diffusion du monoxyde de carbone (DLCO). Conclusion Nous decrivons l’evolution d’une presentation rare de la MDCL pulmonaire isolee sous la forme de bronchectasies kystiques diffuses, a parois fines, non secretantes, s’associant a une destruction kystique du parenchyme pulmonaire. L’hypothese d’une MDCL pulmonaire doit etre evoquee devant des bronchectasies atypiques d’etiologie indeterminee.

Chronic obstructive pulmonary disease, a disease of increasing incidence, is related mainly to smoking. Although symptoms only appear at adulthood, the disease can develop from early life events. For example, bronchopulmonary dysplasia, which occurs in preterm infants, is characterized by airspace enlargement and could lead to late lung consequences. Once the lesions are established, no curative treatment is available. Stimulating lung regeneration from endogenous stem cells is therefore an exciting research domain, particularly through the activation of the mesenchymal contingent located in the lung stem cell niche., La bronchopneumopathie chronique obstructive, affection d’incidence croissante, est liée principalement au tabagisme. Bien que les symptômes n’apparaissent qu’à l’âge adulte, la maladie peut se développer à partir d’événements précoces de la vie. La dysplasie bronchopulmonaire, par exemple, survenant chez le nouveau-né prématuré, est caractérisée par un élargissement des espaces aériens et peut avoir des conséquences pulmonaires tardives. Une fois les lésions établies, aucun traitement curatif n’est disponible. Stimuler la régénération pulmonaire à partir de cellules souches endogènes est donc une perspective de recherche séduisante, notamment par le biais de l’activation du contingent mésenchymateux présent dans la niche des cellules souches pulmonaires.

Introduction La recente decouverte des addictions oncogeniques a radicalement modifie la prise en charge du cancer bronchopulmonaire avance via le developpement des therapies ciblees par inhibiteurs de tyrosine kinase. Notre etude avait pour objectifs l’estimation de la repartition des principales addictions oncogeniques et l’etude de leur impact pronostique chez les patients suivis au CHRU de Nancy pour un adenocarcinome bronchopulmonaire d’emblee metastatique. Methodes Une analyse retrospective incluant 114 patients qui presentaient un adenocarcinome bronchopulmonaire metastatique diagnostique au CHRU de Nancy entre 2012 est 2014 a ete realisee afin d’etudier la survie a 5 ans. Resultats La repartition des addictions oncogeniques dans notre population, comparable a celle obtenue sur le plan national [1] , etait la suivante : KRAS (27,2%), puis EGFR (13,2%), et enfin BRAF (4,4%) et ALK (1,8%) ( Tableau 1 ). Le pronostic de l’adenocarcinome bronchopulmonaire metastatique restait sombre avec une survie a 5 ans Conclusion La repartition des addictions oncogeniques dans l’adenocarcinome bronchopulmonaire au CHRU de Nancy, comprenant une majorite de patients mutes KRAS, semble superposable aux donnees de la litterature pour les populations d’Europe Occidentale. La mutation EGFR semble conferer un avantage pronostique, en grande partie explique par l’efficacite des therapies ciblant cette alteration moleculaire.

The Société de Pneumologie de Langue Française proposes a decision algorithm on long-term pharmacological COPD treatment. A working group reviewed the literature published between January 2009 and May 2016. This document lays out proposals and not guidelines. It only focuses on pharmacological treatments except vaccinations, smoking cessation treatments and oxygen therapy. Any COPD diagnosis, based on pulmonary function tests, should lead to recommend smoking cessation, vaccinations, physical activity, pulmonary rehabilitation in case of activity limitation, and short-acting bronchodilators. Symptoms like dyspnea and exacerbations determine the therapeutic choices. In case of daily dyspnea and/or exacerbations, a long-acting bronchodilator should be suggested (beta-2 agonist, LABA or anticholinergics, LAMA). A clinical and lung function reevaluation is suggested 1 to 3 months after any treatment modification and every 3-12 months according to the severity of the disease. In case of persisting dyspnea, a fixed dose LABA+LAMA combination improves pulmonary function (FEV1), quality of life, dyspnea and decreases exacerbations without increasing side effects. In case of frequent exacerbations and a FEV1≤70%, a fixed dose long-acting bronchodilator combination or a LABA+ inhaled corticosteroids (ICS) combination can be proposed. A triple combination (LABA+LAMA+ICS) is indicated when exacerbations persist despite one of these combinations. Dyspnea in spite of a bronchodilator combination or exacerbations in spite of a triple combination should lead to consider other pharmacological treatments (theophylline if dyspnea, macrolides if exacerbations, low-dose opioids if refractory dyspnea).

Resume Introduction Le deficit en alpha-1 antitrypsine est une maladie hereditaire definie par une concentration serique d’alpha-1 antitrypsine inferieure a 11 μM/L. L’allele le plus courant est l’allele PI M et les alleles deficitaires les plus frequents sont les alleles PI S et PI Z. Les alleles PI Null donnent lieu a des concentrations indetectables d’alpha-1 antitrypsine circulante. La suspicion d’un allele PI Null requiert l’utilisation de techniques diagnostiques adaptees. Observation Nous rapportons le cas d’un patient de 33 ans presentant une dyspnee d’effort et un trouble ventilatoire obstructif modere non reversible. Le tabagisme etait inferieur a 3 paquets-annees. Le scanner thoracique montrait un emphyseme panlobulaire diffus. La concentration serique d’alpha-1 antitrypsine etait effondree. Le phenotypage par focalisation isoelectrique en gel d’agarose ne montrait aucune bande. L’etude du gene SERPINA1 , par PCR-sequence des exons II, III, IV et V et les sequences introniques flanquantes, revelait un allele NullQ0o urem a l’etat homozygote. Le cas index presentait une aggravation rapide du trouble ventilatoire obstructif. Conclusion Dans le cas d’un deficit en alpha-1 antitrypsine serique, l’analyse du phenotype de la proteine par isoelectrofocalisation doit etre realisee en premiere intention. La mise en evidence d’un profil atypique doit faire evoquer la presence d’alleles deficitaires autres que PI S et PI Z qui ne peuvent etre caracterises que par sequencage complet du gene SERPINA1 . Les patients porteurs d’une mutation Null ont un risque eleve de bronchopneumopathie chronique obstructive severe.

The transcription factor p53 is overexpressed in the lung of patients with emphysema, but it remains unclear if it has a deleterious or protective effect in disease progression. We investigated the role of p53 in the elastase-induced emphysema model and the molecular underlining mechanisms. Wild-type (WT) and p53(-/-) mice were instilled with pancreatic porcine elastase. We quantified emphysema (morphometric analysis), chemokine (C-C motif) ligand 2 (CCL2), and TNF-α in bronchoalveolar lavage (BAL) (ELISA), oxidative stress markers [heme oxygenase 1 (HO1), NAD(P)H dehydrogenase quinone 1 (NQO1), and quantitative RT-PCR], matrix metalloproteinase 12 (MMP12) expression, and macrophage apoptosis (cleaved caspase-3, immunofluorescence). p53 gene expression was up-regulated in the lung of elastase-instilled mice. p53 deletion aggravated elastase-induced emphysema severity, pulmonary inflammation (macrophage and neutrophil numbers and CCL2 and TNF-α levels in BAL), and lung oxidative stress. These findings, except for the increase in CCL2, were reproduced in WT mice transplanted with p53(-/-) bone marrow cells. The increased number of macrophages in p53(-/-) mice was not a consequence of reduced apoptosis or an excess of chemotaxis toward CCL2. Macrophage expression of MMP12 was higher in p53(-/-) mice compared with WT mice after elastase instillation. These findings provide evidence that p53(-/-) mice and WT mice grafted with p53(-/-) bone marrow cells are more prone to developing elastase-induced emphysema, supporting a protective role of p53, and more precisely p53 expressed in macrophages, against emphysema development. The pivotal role played by macrophages in this phenomenon may involve the MMP12-TNF-α pathway.

Introduction L’objectif de cette etude retrospective etait de comparer la survie et la tolerance des inhibiteurs de tyrosine kinase (ITK) de premiere et de seconde generation chez des patients atteints d’adenocarcinomes bronchiques metastatiques mutes EGFR non selectionnes rencontres en pratique courante. Methodes Dans cette etude multicentrique, les donnees de tous les patients atteints d’adenocarcinome de stade IV mute EGFR et traites par ITK (1re ou 2e generation) entre 2010 et 2018 ont ete revues. Les patients ont ete assignes en 2 groupes : ITK de 1re generation (erlotinib et gefitinib) vs ITK de 2e generation (afatinib). La survie a ete evaluee a l’aide d’un test du Log-rank et du modele a risque proportionnel de Cox. Resultats Deux cent soixante-huit patients ont ete inclus dont 221 (82,5 %) traites par ITK de 1re generation et 47 (17,5 %) par afatinib. Dans les 2 groupes, l’âge median des patients etait similaire (68,40 ans [IQR : 8,28] vs 68,43 ans [IQR : 6,54], p = 0,89), de meme que la proportion de femmes (82,4 % vs 87,2 %, p = 0,42). Les patients du groupe afatinib etaient plus alteres sur le plan general (PS ≥ 2 : 21,3 % vs 13,6 %, p = 0,004), avaient une maladie plus avancee (stade M1b ou M1c : 80,9 % vs 63,3 %, p = 0,004) avec plus de metastases cerebrales, et etaient porteurs de mutations plus rares (25,5 % vs 5,5 %, p Conclusion Dans cette etude, il n’a pas ete mis en evidence de benefice de l’afatinib, comparativement aux ITK de 1re generation en termes de survie chez les patients fragiles.

Introduction L’immunotherapie est le standard de traitement en 2e intention des carcinomes bronchiques non a petites cellules. L’objectif de ce travail est d’evaluer si les differentes substitutions d’acide amine de Kirsten rat sarcoma viral oncogene homolog (KRAS) sont des facteurs pronostiques de reponse a l’immunotherapie chez les patients porteurs d’un adenocarcinome pulmonaire en recidive. Methodes Etude retrospective, multicentrique, de patients porteurs d’adenocarcinomes pulmonaires de stade III ou IV, en recidive, dont le statut mutationnel etait connu, et traites par immunotherapie entre 2015 et 2018. Les criteres de jugement etaient la survie globale (SG), la survie sans progression (SSP), la reponse tumorale selon les criteres RECIST, et la tolerance du traitement. Resultats Parmi les 674 patients, 248 (36,8 %) avaient une mutation KRAS, essentiellement du codon 12 (n = 240, 96,8 %), et 426 (63,2 %) etaient KRAS wild type (WT). Les 2 groupes etaient comparables en termes d’âge (âge median de 64,04 ans) et de sexe (65,9 % d’hommes). Le groupe KRAS presentait moins de cancers de stade IV (n = 212, 85,5 %) et de metastases cerebrales (n = 52, 21 %) que le groupe WT (stade IV : n = 402, 94,4 %, p Conclusion Les transversions G12 V et G12D de KRAS seraient un facteur predictif de bonne reponse a l’immunotherapie chez les patients suivis pour un adenocarcinome pulmonaire en recidive.

Resume Introduction Dans l’hypertension arterielle pulmonaire (HTAP), plusieurs traitements agissant sur la dysfonction de l’endothelium pulmonaire ont prouve leur efficacite. L’exposition a la fumee de cigarette provoque une dysfonction endotheliale comparable a celle observee chez les patients atteints d’HTAP. L’objectif principal etait d’investiguer la difference de changement hemodynamique a l’exercice de patients sous traitement specifique, entre le diagnostic (T0) et la premiere reevaluation comprenant un catheterisme cardiaque droit (T1), entre les exposes ou non a la fumee de cigarette. Methodes Entre 2002 et 2018, nous avons recueilli le statut tabagique des patients atteints d’hypertension pulmonaire du groupe 1 ou du groupe 4 sous traitement specifique ayant realise une epreuve d’effort a T0 et a T1. Resultats Au sein des 109 patients inclus, il n’y avait pas de difference significative entre les 2 groupes a T0. La difference de PAPm isodebit a l’exercice entre T0 et T1 dans le groupe « exposes » etait de 19,0 ± 15,4 mmHg versus 21,3 ± 16,6 mmHg dans le groupe non expose (p = 0,59). Discussion Notre etude n’a pas montre de difference concernant l’evolution hemodynamique a l’exercice entre les exposes ou non a la fumee de cigarette. L’action endotheliale du tabagisme ne semble pas avoir d’impact sur la reponse au traitement specifique de l’HTAP.

International audience; To study vertebral fracture (VF) prevalence and the scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1) on computed tomography scans (CT-scans) in systemic sclerosis patients. This monocentric retrospective study included patients followed from 2000 to 2014 and fulfilling ACR/EULAR 2013 criteria for systemic sclerosis and who underwent a thoracic or thoraco-abdomino-pelvic CT-scan during their follow-up. Clinical characteristics for sclerosis and osteoporosis risk factors were collected. For CT-scan, the VFs were determined according to Genant’s classification, the SBAC-L1 was measured in Hounsfield Units (HU), and a SBAC-L1 ≤ 145 HU (fracture threshold) defined patients at VF risk. Predictive factors for SBAC-L1 ≤ 145 HU were studied. A total of 70 patients were included [mean age, 62.3 (± 15.6) years, women 88.5%, diffuse sclerosis 22.9% (n = 16)]. On CT-scans, three VFs were detected in three patients (4.3%). The mean SBAC-L1 was 157.26 HU (± 52.1), and 35 patients (50%) presented a SBAC-L1 ≤ 145 HU. In multivariate analysis, only age (especially patients older than 63 years, OR = 1.08, CI 95% 1.04–1.13, p = 0.001) and calcinosis (OR = 6.04, CI 95% 1.27–28.70, p = 0.02) were independently associated with a SBAC-L1 ≤ 145 HU. On a large sample of patients with systemic sclerosis, the VF prevalence on CT-scan was low (4.3%) while 50% of the patients presented a SBAC-L1 ≤ 145 HU. Interestingly, the presence of calcinosis, periarticular calcifications or acro-osteolysis was linked with low SBAC-L1 and should lead to an osteoporosis screening, especially for patients under 63 years old.

Introduction: Pulmonary emphysema is an aging-related disease. However, the mechanisms underlying this phenomenon still remain poorly unknown. P16Ink4 is a key factor implicated in aging-related diseases. Whether p16 is involved in elastase-induced emphysema in mice remains to be determined. Aim: To determine if p16 deletion protects against elastase-induced emphysema in mice. Methods: Wild-type (WT) and p16-/- mice were instilled with pancreatic porcine elastase and sacrificed three weeks or three months later to address the degree of emphysema (morphometric analysis), alveolar septal thickness, collagen deposition (sirius red) and myofibroblasts content (α smooth muscle actin immunostaining). Results: Three weeks after instillation, elastase induced airspace enlargement in the same way in WT and p16-/- mice. However, three months later, elastase-instilled WT mice showed airspace enlargement and, without modification of collagen deposition while elastase-instilled p16-/- mice have reduced airspace enlargement, and increased septal thickness with enhanced collagen deposition, and more myofibroblasts. Conclusions: p16-/- mice are not immediately but later protected against elastase-induced emphysema, and develop a concomitant alveolar fibrosis suggesting a process of repair partially defective.

Haemodynamic follow up in pulmonary arterial hypertension (PAH) is currently based on right heart catheterisation (RHC). The primary objective of the EVITA study is to compare the use of cardiac magnetic resonance imaging (cMRI) with RHC in the identification of an unfavourable hemodynamic status. The secondary objectives are to determine the role of cMRI in the follow up process. Patients will undergo at diagnosis and at follow up visits both RHC and cMRI. Patients will be followed and treated according to the current guidelines. The primary endpoint will be an unfavourable haemodynamic status defined by cardiac index

Mild-to-moderate pulmonary hypertension is a common complication of chronic lung diseases. Very few patients have severe pulmonary hypertension; if that is the case, it may be due to co-morbidities or correspond to a particular phenotype. Although pulmonary hypertension has little or no involvement in exercise limitation, it is an independent prognostic factor for survival. The first stage of diagnosis of pulmonary hypertension in chronic lung disease is to establish a level of high, intermediate, or low probability using Doppler echocardiography according to the European Society of Cardiology/European Respiratory Society Guidelines. To determine the cause of pulmonary hypertension, it may be necessary to perform a comprehensive search for the most frequent respiratory and cardiovascular diseases. There are few, but important, indications for right heart catheterization in chronic lung diseases. The main indications are candidates for lung transplantation, suspicion of pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension, and when pulmonary haemodynamics are likely to have significant therapeutic implications. The underlying respiratory disease or associations of diseases should be treated according to current guidelines before concluding that a patient has severe pulmonary hypertension. Non-invasive ventilation and long-term oxygen therapy in hypercapnic and hypoxaemic patients, respectively, improve pulmonary haemodynamics. With the exception of cardiovascular co-morbidities, pharmacotherapies for high blood pressure and for left heart diseases are not recommended to treat pulmonary hypertension due to chronic lung diseases. Pulmonary arterial hypertension-approved therapies are not recommended in pulmonary hypertension due to chronic lung diseases.