Stable long-term pulmonary function after fludarabine, antithymocyte globulin and i.v. BU for reduced-intensity conditioning allogeneic SCT.

International audienceLung function decline is a well-recognized complication following allogeneic SCT (allo-SCT). Reduced-intensity conditioning (RIC) and in vivo T-cell depletion by administration of antithymocyte globulin (ATG) may have a protective role in the occurrence of late pulmonary complications. This retrospective study reported the evolution of lung function parameters within the first 2 years after allo-SCT in a population receiving the same RIC regimen that included fludarabine and i.v. BU in combination with low-dose ATG. The median follow-up was 35.2 months. With a median age of 59 years at the time of transplant, at 2 years, the cumulative incidences of non-relapse mortality was as low as 9.7%. The cumulative incidence of relapse was 33%. At 2 years, the cumulative incidences of extensive chronic GVHD (cGVHD) and of pulmonary cGVHD were 23.1% and 1.9%, respectively. The cumulative incidences of airflow obstruction and restrictive pattern were 3.8% and 9.6%, respectively. Moreover, forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio remained stable from baseline up to 2 years post transplantation (P=0.26, P=0.27 and P=0.07, respectively). These results correspond favorably with the results obtained with other RIC regimens not incorporating ATG, and suggest that ATG may have a protective pulmonary role after allo-SCT

Mesenchymal Stem Cells Induce Suppressive Macrophages through Phagocytosis in a Mouse Model of Asthma

International audienceac‐ cepted for publication February 01, 2016; available online without sub‐ scription through the open access option. ©AlphaMed Press 1066‐5099/2016/$30.00/0 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typeset‐ ting, pagination and proofreading process which may lead to differ‐ ences between this version and the Version of Record. Please cite this article as 1,2,3,4 Key words. house dust mite asthma mesenchymal stem cells M2 macro‐ phage airway hyper‐responsiveness phagocytosis airway smooth muscle contraction. ABSTRACT Mesenchymal stem cell (MSC) immunosuppressive functions make them attractive candidates for anti‐inflammatory therapy in allergic asthma. However the mechanisms by which they ensure therapeutic effects remain to be elucidated. In an acute mouse model of house dust mite (Der f)‐ induced asthma, one i.v. MSC injection was sufficient to normalize and stabilize lung function in Der f‐sensitized mice as compared to control mice. MSC injection decreased in vivo airway responsiveness and de‐ creased ex vivo carbachol‐induced bronchial contraction, maintaining bronchial expression of the inhibitory type 2 muscarinic receptor. To eval‐ uate in vivo MSC survival, MSCs were labelled with PKH26 fluorescent marker prior to i.v. injection, and 1 to 10 days later total lungs were digest‐ ed to obtain single‐cell suspensions. 91.5 ± 2.3% and 86.6 ± 6.3% of the recovered PKH26 + lung cells expressed specific macrophage markers in control and Der f mice respectively, suggesting that macrophages had phagocyted in vivo the injected MSCs. Interestingly, only PKH26 + macro‐ phages expressed M2 phenotype, while the innate PKH26 ‐ macrophages expressed M1 phenotype. Finally, the remaining 0.5% PKH26 + MSCs ex‐ pressed 10 to 100 fold more COX‐2 than before injection, suggesting in vivo MSC phenotype modification. Together, the results of this study indicate that MSCs attenuate asthma by being phagocyted by lung macrophages, which in turn acquire a M2 suppressive phenotype. STEM CELLS 2016; 00:000–000 SIGNIFICANCE STATEMENT In a model of asthma, injected mesenchymal stem cells (MSCs) are in vivo phagocyted by lung macrophages in the next 24 hours following i.v. injec‐ tion. Lung macrophages that have phagocyted MSCs, in turn, acquire an im‐ munosuppressive phenotype, responsible for MSC anti‐inflammatory in vivo efficacy

An observational study of anaerobic bacteria in cystic fibrosis lung using culture dependant and independent approaches

International audienceAbstract Strict anaerobes are undeniably important residents of the cystic fibrosis (CF) lung but are still unknowns. The main objectives of this study were to describe anaerobic bacteria diversity in CF airway microbiota and to evaluate the association with lung function. An observational study was conducted during eight months. A hundred and one patients were enrolled in the study, and 150 sputum samples were collected using a sterile sample kit designed to preserve anaerobic conditions. An extended-culture approach on 112 sputa and a molecular approach (quantitative PCR targeting three of the main anaerobic genera in CF lung: Prevotella, Veillonella, and Fusobacterium ) on 141 sputa were developed. On culture, 91.1% of sputa were positive for at least one anaerobic bacterial species, with an average of six anaerobic species detected per sputum. Thirty-one anaerobic genera and 69 species were found, which is the largest anaerobe diversity ever reported in CF lungs. Better lung function (defined as Forced Expiratory Volume in one second > 70%) was significantly associated with higher quantification of Veillonella . These results raise the question of the potential impact of anaerobes on lung function

Immune alveolitis in interstitial lung disease: an attractive cytological profile in immunocompromised patients

International audienceBackground: Bronchoalveolar lavage (BAL) is a major diagnostic tool in interstitial lung disease (ILD). Its use remains largely quantitative, usually focused on cell differential ratio. However, cellular morphological features provide additional valuable information. The significance of the "immune alveolitis" cytological profile, characterized by lymphocytic alveolitis with activated lymphocytes and macrophages in epithelioid transformation or foamy macrophages desquamating in cohesive clusters with lymphocytes, remains unknown in ILD. Our objective was to describe patients' characteristics and diagnoses associated with an immune alveolitis profile in undiagnosed ILD. Methods: We performed a monocentric retrospective observational study. Eligible patients were adults undergoing diagnostic exploration for ILD and whose BAL fluid displayed an immune alveolitis profile. For each patient, we collected clinical, radiological and biological findings as well as the final etiology of ILD. Results: Between January 2012 and December 2018, 249 patients were included. Mean age was 57 ± 16 years, 140 patients (56%) were men, and 65% of patients were immunocompromised. The main etiological diagnosis was Pneumocystis pneumonia (PCP) (24%), followed by drug-induced lung disease (DILD) (20%), viral pneumonia (14%) and hypersensitivity pneumonitis (HP) (10%). All PCP were diagnosed in immunocompromised patients while HP was found in only 8% of this subgroup. DILD and viral pneumonia were also commonly diagnosed in immunocompromised patients (94% and 80%, respectively). Conclusion: Our study highlights the additional value of BAL qualitative description in ILD. We suggest incorporating the immune alveolitis profile for the diagnosis and management of ILD, especially in immunocompromised patients, since it guides towards specific diagnoses

Recommandations pratiques pour l’utilisation et l’interprétation des tests de détection de l’interféron gamma dans le diagnostic de l’infection tuberculeuse latente et de la tuberculose maladie

International audienc

CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma

International audienceBackgroundOne of the major challenges in managing allergic bronchopulmonary aspergillosis (ABPA) remains consistent and reproducible assessment of response to treatment.Research questionWhat are the most relevant changes in computed tomography (CT-scan) parameters over time for assessing response to treatment?Study Design and MethodsIn this ancillary study of a randomized clinical trial (NEBULAMB), asthmatic patients with available CT-scan and without exacerbation during a 4-month ABPA exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT-scan parameters were assessed by systematic analyses of CT-scan findings at initiation (M0) and end of treatment (M4). CT-scans were assessed by two radiologists blinded to the clinical data. Radiological parameters were determined by selecting those showing significant changes over time. Improvement of at least one, without worsening of the others, defined the radiological response. Agreement between radiological changes, clinical and immunologic responses was likewise investigated.ResultsAmong the 139 originally randomized patients, 132 were included. We identified 5 CT-scan parameters showing significant changes at M4: mucoid impaction extent, mucoid impaction density, centrilobular micronodules, consolidation/ground-glass opacities and bronchial wall thickening (P<0.05). These changes were only weakly associated with one another, except for mucoid impaction extent and density. No agreement was observed between clinical or immunologic and radiological responses, assessed as an overall response, or considering each of the parameters (Cohen’s κ, -0.01 to 0.24).InterpretationChanges in extent and density of mucoid impactions, centrilobular micronodules, consolidation/ground-glass opacities and thickening of the bronchial walls were found to be the most relevant CT-scan parameters to assess radiological response to treatment. A clinical, immunologic and radiological multidimensional approach should be adopted to assess outcomes, probably with a composite definition of response to treatment

Deconditioning, fatigue and impaired quality of life in long-term survivors after allogeneic hematopoietic stem cell transplantation: Altered exercise capacity in allo-HSCT survivors

International audienceLong-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk for treatment-related adverse events, that may worsen physical capacity and may induce fatigue and disability. The aims of this prospective study were to evaluate exercise capacity in allotransplant survivors and its relationship with fatigue and disability. Patient-reported outcomes and exercise capacity were evaluated in 71 non-relapse patients 1 year after allo-HSCT, using validated questionnaires, cardiopulmonary exercise testing (CPET) with measure of peak oxygen uptake (peakVO2) and deconditioning, pulmonary function testing, echocardiography and 6-min walk test. A high proportion (75.4%) of allo-HSCT survivors showed abnormal cardiopulmonary exercise testing parameters as compared to predicted normal values, including 49.3% patients who exhibited moderate to severe impairment in exercise capacity and 37.7% patients with physical deconditioning. PeakVO2 values were not accurately predicted by 6-min walk distances (r = 0.53). Disability and fatigue were strongly associated with decreased peakVO2 values (p = 0.002 and p = 0.008, respectively). Exercise capacity was reduced in most allo-HSCT long-term survivors. Because reduced exercise capacity was associated with fatigue, disability and a decrease in quality of life, cardiopulmonary exercise testing should be performed in every patient who reports fatigue and disability

Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

International audienceRationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Measurements and Main Results: Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV1 = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV1 was +15.1 (+13.8 to +16.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended