High-Dimensional Clinical Data Modeling : Application To Respiratory Diseases

Cette thèse est consacrée à l'application et au développement de méthodes biostatistiques originales pour des applications médicales et cliniques concernant plus particulièrement les pathologies respiratoires. Il s'agit ainsi d'un travail de recherche transversale, visant à la modélisation de données hétérogènes, colinéaires et de grande dimension pour des applications cliniques. Un état de l'art traitant du diagnostic de l'asthme et de hyperactivité bronchique a tout d'abord été dressé, avant de proposer une première application statistique, prenant la forme de modèles de régressions multiples. Ce type de modèle étant particulièrement sensible à la dimension et la colinéarité des données, les chapitres suivants proposent plusieurs améliorations, après avoir explicité en détail l'enjeu et les méthodes actuelles d'analyse de données de grande dimension. Un premier modèle de classification hiérarchique non supervisé a été mis au point et appliqué au cas de la quantification du piégeage aérique. Un algorithme de régression Partial Least Square a également été mis en œuvre, prédisant une ou plusieurs variables Y à partir d'un set de variables X hétérogènes et colinéaires, ce qui a permis de mettre en évidence l'impact de l'âge sur les petites voies aériennes, tout en considérant de nombreux autres paramètres. Enfin, un algorithme d'analyse fractale a été créé, en vue de quantifier en une seule valeur la complexité spatiale et géométrique d'images de scanners thoraciques, cela constituant un innovant outil d'aide au diagnostic radiologique.This thesis outlines new statistic methods devoted to clinical and medical applications, dealing more precisely with respiratory diseases. Our goal was to model and analyze high-dimensional clinical data, often heterogeneous, and collinear. A clinical state of the art of asthma diagnosis and bronchial hyperreactivity was first stated, before proposing a first statistical application, which took the shape of multiple regression models. This type of models is particularly tricky when treating high-dimensional collinear data, which is why the other chapters are an enhancement of this first model. Firstly, a non-supervised hierarchical classification was carried out and applied to air trapping quantification. A Partial Least Square regression model was also executed, allowing prediction of one or more variables from a set of X variables, which allowed us to highlight the impact of age on small airway impairment. Finally, a fractal analysis was performed, in order to quantify the geometrical and spatial complexity of a CT scan image into a single value. This kind a prospective methodology, where the statistics are directly involved in the clinical work, represents a brand new tool which can help medical diagnosis

Increased neutrophil surface PD-L1 expression in tobacco smokers

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k-Nearest Neighbor Curves in Imaging Data Classification

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Asthma, COPD, and overlap in a national cohort: ACO on a gradient

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Impact of a medico-pharmaceutical follow-up and an optimized communication between hospital and community on the readmission to the emergency department for an adverse drug event: URGEIM, study protocol for a randomized controlled trial

International audienceBackground Adverse drug events (ADE) represent one of the main causes of admission to emergency department (ED). Their detection, documentation, and reporting are essential to avoid readmission. We hypothesize that a pharmacist-initiated multidisciplinary transition of care program combining ED pharmacist contribution and medications’ data transfer between inpatient and outpatient caregivers will reduce emergency visits related to ADEMethod/design This is a prospective, open-label, randomized controlled trial. The primary aim of the study is 6-month ED readmission related to the same ADE. Three hundred forty-six adult patients with an ADE detected by a binomial pharmacist-physician will be recruited from the ED of an University Hospital and will be randomized in two groups: [1] experimental group (multidisciplinary transition of care program and medications’ data transfer between inpatient and outpatient caregivers) and [2] control group (usual care). Patients will be followed up over a period of 6 months. Endpoints will be carried out blindly of the randomization arm. The primary endpoint is the rate of patients who had at least one readmission in the ED for the same reason at 6 months (data collected during a phone call with the patient and the general practitioner). Trials registered NCT03725046.Discussion The trial results will have implications for the role of the clinical pharmacist in an emergency department. If successful, the intervention could be considered for implementation across other hospitals.Trial registration ClinicalTrials.gov NCT03725046 . Registered on 30 October 201

Clinical Study Distal Airway Impairment in Obese Normoreactive Women

Background. Asthma-like symptoms are frequent in overweight and obesity, but the mechanism is unclear when airway hyperresponsiveness (AHR) is lacking. In this study, we focused on obese women with a clinical suspicion of asthma but negative methacholine challenge and tested distal airway hyperreactivity, explored by Forced Vital Capacity dose-response slope (FVC DRS). Objective. To question AHR at the distal airway level in obese women. Methods. A total of 293 symptomatic obese and nonobese women free of treatment were investigated. Methacholine challenge tests were undertaken, and patients were divided according to their results to the test. In hyperreactive and nonhyperreactive patients and in our total population, correlations, regression analyses, and analyses of covariance were performed to compare distal airway hyperreactivity in three groups of body mass index (BMI). Results. After adjusting for age and baseline respiratory values, the relationship between FVC and FEV1 (forced expiratory volume in one second) DRS was influenced by BMI, with a lower slope in obese than overweight and normal patients in our total population ( = 0.008) and in our nonhyperreactive one ( = 0.028). Conclusion. Distal airway hyperresponsiveness was observed in symptomatic wheezing obese women negative to methacholine challenge

Impact of psychological factors on the health-related quality of life of patients treated for pulmonary arterial hypertension

International audiencePulmonary arterial hypertension (PAH) is a rare and life-threatening disease well-marked by under diagnosis, delayed diagnosis and atypical treatments. Few data are available on the quality of life (QoL) and psychosocial characteristics of patients with PAH. Our aim is to describe the impact of psychological factors on the health-related quality of life (HRQoL) of treated PAH patients in a cross-sectional study

Semaphorins: From Angiogenesis to Inflammation in Rheumatoid Arthritis

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Identification of the larval serum proteins as major fruit fly ( Drosophila melanogaster ) occupational allergens

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Club cell secretory protein serum concentration is a surrogate marker of small-airway involvement in asthmatic patients

International audiencePoor asthma control and recurrent exacerbations have been shown to be a phenotypic counterpart of asthma with predominantly small-airway involvement.1 Biomarkers are not always accurate in asthmatic patients, especially in serum, because compartmentalization can occur between the blood and airways. Blood eosinophil counts do not represent an overall view of airway inflammation, and exhaled nitric oxide measurements at different flow rates (fraction of exhaled nitric oxide [Feno] and alveolar nitric oxide [Calvno]) have been developed and validated to reflect more accurately proximal and distal airway inflammation.2Club cell secretory protein (CCSP) serum concentration has been shown to be associated with chronic obstructive pulmonary disease, bronchiolitis obliterans syndrome, and sarcoidosis, which are all predominantly diseases involving the small airways. Ranges of CCSP concentrations in healthy subjects, reproducibility, and relationships between serum and airway levels are known and can be used as potential surrogate markers. Our aim was to assess small-airway disease in asthmatic patients and to find a related biomarker. We used a dynamic assessment of gas trapping using computed tomographic (CT) imaging of the chest during methacholine challenge as a marker of small-airway disease