University Hospitals of Tours

The morbi-mortality and social cost of addictive disorders led the French authorities to set up a government plan in 2018 to combat drugs and addictive behavior (Interministerial mission to combat drugs and addictive behaviour - (MILDECA)). In particular, it encourages early detection, which is the first stage in a validated global approach to the management of addictive disorders. Improving early identification of addictive disorders in primary care would reduce morbidity and mortality and improve quality of life for patients with addictive disorders. The identification of use disorders should be systematic in primary care and was the subject of a recommendation in 2015. Numerous tests are cited in these recommendations, but few have actually been validated in primary care, and none has been shown to be feasible. For example, only 23% of GPs claim to systematically identify alcohol consumption.
Other primary care professionals (physiotherapists, nurses, midwives, dentists, pharmacists) also have a role to play in identifying addictive disorders. The evolution of their respective professions (delegation of tasks, creation of the profession of advanced practice nurse, medical assistants) and the recent reorganization of the practice framework, both in terms of practice structures and professional community organizations, involve them in a global multidisciplinary collaboration on patient care, particularly in the early identification of addictive disorders.
The hypothesis is that the difficulties in implementing tests to identify addictive disorders in primary care are linked to the lack of specific consideration of the needs of primary care patients and caregivers.
The overall aim of the study is to improve the early detection of addictive disorders through brief training for primary care healthcare professionals.

Viral pneumonia, including SARS-CoV-2 and influenza A virus (IAV), can culminate in acute respiratory distress syndrome (ARDS), a severe form of respiratory failure with high mortality. Uncontrolled local inflammatory response and impaired tissue repair are hallmarks of ARDS. However, lack of in-depth understanding of the immunopathology lead to limited identification of potential 'endotypes' who may benefit from individualized targeted therapies. Mucosal Associated Invariant T (MAIT) cells represent a peculiar lineage of T cells with a wide panel of effector functions. Thus, they emerge as potential key players and appealing targets in ARDS through their potent abilities to modulate immune response at barrier sites and promote tissue repair. Recent data from the investigators and others indicated that MAIT cells are highly activated in patients with Sars-Cov-2 and IAV ARDS, but the associated activation mechanisms and precise functions remain unknown.
In this context, the investigators aim at investigating the implication and potential harnessing of MAIT cells in severe viral pneumonias and associated ARDS by with a dedicated clinical study. First, the investigators will perform a comprehensive and longitudinal phenotyping of immune response during viral pneumonia-induced ARDS, including MAIT cells, in blood -and airway compartment for mechanically ventilated patients. To provide more insight into specificity of virally induced pneumonia and ARDS, longitudinal phenotyping of immune response of patients with bacterial pneumonia, and control patients with unrelated ARDS (severe trauma, pancreatitis or major surgery) will also be performed.

Context. Non cystic fibrosis bronchiectasis (NCFB) is a group of suppurative chronic airway diseases of multiple causes. Bronchiectasis is characterized by an abnormal, irreversible dilatation of the bronchi, airway obstruction, chronic cough, and sputum production. Inhaled polyclonal immunoglobulin G (IgG) is a new therapeutic approach for NCFB. Inhaled IgG is expected to have beneficial effects due to its ability to reduce the range of respiratory pathogens capable of infecting the respiratory tract, decrease the pulmonary load of existing bacterial populations, improve mucociliary clearance by restoring epithelial cell functions, and decrease lung inflammation. Pre-clinical data packages showed that IgG reduced the airway pathogen load and related cell damage after infection in rodents and non-human primates. The aim of this study is collect information on the impact of NFCB airway mucus on the biological barriers to locally delivered IgG.
Study design. Thirty patients with stable NFCB will be recruited. The patients will provide induced sputum samples after inhaling isotonic saline. Induced sputum will be used for 1) identification of colonizing bacteriological, fungal and virological populations and 2) for in vitro pharmacological experiments.
The main outcome is the quantification by whole-cell ELISA of binding to Pseudomonas aeruginosa by a polyclonal IgG in the presence of mucus derived from the sputum of NCFB patients.
Secondary outcomes are (1) the measurement of proteolysis, by Western-Blot, of exogenous polyclonal IgG added in the mucus derived from sputum of NCFB patients. The results will be expressed as a percentage of integrity over the one obtained when the polyclonal IgG is added in saline solution and will be compared with in vitro results; (2) the measurement of mobility by Fluorescence Recovery After Photobleaching (FRAP) of exogenous fluorescently-labelled polyclonal IgG added in the mucus derived from sputum of NCFB patients. The results will include the determination of the t(1/2), mobile and immobile fractions over the one obtained when the polyclonal IgG is added in saline solution and will be compared with in vitro results; (3) impact of microbial airway colonization on IgG binding, proteolysis and Ig mobility. Samples with microbial colonization (either bacterial, viral or fungal) will be compared with uncolonized samples.
This project will help in decision-making in the development of inhaled antibody therapeutics. Specifically, the study will provide information on the capacity of locally applied polyclonal IgG to diffuse through mucus and bind to pathogens.