Active clinical trials for "Lung Diseases"

Sepsis leads to a deregulated host response that can lead to organ failure. During sepsis, experimental and clinical data suggest the occurrence of mitochondrial dysfunctions, particularly in circulating muscle and monocytes, which may contribute to organ failure and death. Lower respiratory infection is the leading cause of death from infectious causes. Mechanical ventilation (MV) is required in 20% of cases of bacterial pneumopathy with Streptococcus pneumoniae (S.p.) , with mortality reaching 50%. There are then frequently criteria for acute respiratory distress syndrome (ARDS), combining bilateral lung involvement and marked hypoxemia. Cyclic stretching of lung cells induced by MV causes sterile inflammation and tissue damage (i.e. ventilator-induced lung injury [VILI]), which can cause cellular dysfunction that alter the immune response, particularly during ARDS. This is why the application of a so-called protective MV is then required. However, this does not prevent about one-third of patients from showing signs of alveolar overdistension, as evidenced by an increase in motor pressure (MP) (MP≥ 15 cmH2O), associated with an increase in mortality. The deleterious effects of MV could be explained by the occurrence of mitochondrial abnormalities. Indeed, the cyclic stretching of lung cells leads to dysfunction in the respiratory chain and the production of free oxygen radicals (FOS), altering membrane permeability. These phenomena could promote VILI, facilitate the translocation of bacteria from the lung to the systemic compartment and lead to alterations in immune response. In our model of S.p. pneumopathy in rabbits, animals on MV develop more severe lung disorders (lack of pulmonary clearance of bacteria, bacterial translocation in the blood, excess mortality), compared to animals on spontaneous ventilation (SV). Intracellular pulmonary mitochondrial DNA (mtDNA) concentrations, a reflection of the mitochondrial pool, are significantly decreased in ventilated rabbits compared to SV rabbits and in infected rabbits compared to uninfected rabbits. At the same time, the mitochondrial content of circulating cells decreased early (H8) in all infected rabbits, but was only restored in rabbits in SV, those who survived pneumonia (Blot et al, poster ECCMID 2015, submitted article). These data suggest an alteration in the mechanisms that restore mitochondrial homeostasis (mitochondrial biogenesis and mitophagy) during the dual infection/MV agression, which may explain the observed excess mortality. Other work by our team illustrates the importance of these phenomena by showing in a mouse model of polymicrobial infection that inhibition of mitophagia in macrophages promotes survival (Patoli et al, in preparation). Human data on this subject are non-existent. The phenomena of mitochondrial dysfunction nevertheless deserve to be explored in humans during the combined MV/pneumopathy aggression in order to understand its possible impact on the effectiveness of the host's immune response. In a personalized medicine approach, these data would open up prospects for targeted therapies, capable of activating mitochondrial biogenesis and/or modulating mitophagia, to prevent organ dysfunction and mortality during severe CALs treated with antibiotic therapy.

Chronicle obstructive pulmonary disease is a worldwide cause of mortality and morbidity. This systemic disease progressively leads to dyspnea, muscle wasting and exercise capacity impairment. Pulmonary rehabilitation is a cornerstone in the management of these systemic effects. Unfortunately, access to pulmonary rehabilitation is limited for many people who would benefit from it, primarily because of a lack of pulmonary rehabilitation and assessment centers. Optimal assessment should include an incremental cardiopulmonary exercise testing. This test allows to evaluate the factors contributing to exercise intolerance by linking performance and physiological parameters to the underlying metabolism. Moreover, it is the standard test to determine both the optimal training settings as well as any cardiopulmonary contraindications to pulmonary rehabilitation. However, this test is not available in most centers and when it is, consultations are limited. Therefore, pulmonary rehabilitation is often delayed for several weeks and patients can lose motivation. In order to promote pulmonary rehabilitation, the incremental cardiopulmonary exercise testing could be replaced by field tests to individualize pulmonary rehabilitation prescription. The six-minute stepper test is a new field tool. Its sensitivity and reproducibility have previously been reported in patients with chronicle obstructive pulmonary disease. It is easy to set up in the clinical setting and could be used to individualize pulmonary rehabilitation. The main drawback when using field test is that they only provide a non specific assessement of the functional capacity because cardiopulmonary parameters and gaz exchanges are not monitored. Although the performance during the 6-minute stepper test is moderately related with the maximal oxygen consumption during the incremental cardiopulmonary exercise testing performed on a cycloergometer, a direct comprehensive comparison of cardiopulmonary parameters and gaz exchanges during these two tests have never been performed. Moreover, stepping is more closely related with activities of daily life (requiring a repetitive transition from rest to submaximal exercise intensity) than the maximal incremental exercise on cycloergometer and could provide further insight on the disability of patients during their usual activities, such as stair climbing (which is frequently avoided). Additionally, on-transient phase two oxygen consumption kinetic is particularly relevant because it evaluation is independent of the patient's motivation or criteria used to terminate exercise. Therefore, the aim of this study is to compare the cardiorespiratory parameters, the gaz exchanges and the maximality between the six-minute stepper test and the incremental cardiopulmonary exercise testing performed on a cycloergometer. The secondary objective was to compare the on-transient oxygen consumption phase two kinetic parameters (time constant, span and steady state) according to the severity of the disease.

Spirometry is the most commonly used modality for measuring lung function. However, spirometry is a coordination-dependent test and may lead to erroneous results if subjects are unable to fully comply with the instructions. It also lacks the capability for regional assessment of pulmonary functions. Electrical impedance tomography (EIT) is a potential alternative test to spirometry. EIT has been employed in clinical use to provide qualitative and quantitative measurements of ventilation in patients on mechanical ventilators to prevent lung damage or patient-ventilator desynchronies. In this study, we aim to utilize EIT lung device to study EIT-derived indicators in pulmonary functional assessment and develop novel biomarkers for detecting and monitoring pulmonary diseases. This is a non-interventional clinical study on patients with chronic lung diseases, to establish the feasibility of using EIT-lung device in detecting lung functional changes. Specifically, we will establish the relationship between EIT-derived functional indicators and spirometry results. Furthermore, we will explore, develop, and establish EIT-derived regional lung functional indicators in healthy and chronic diseased states. Subjects with underlying lung disease, and age- and gender-matched healthy control subjects will be recruited in this study. They will perform spirometry and EIT examination, as well as an interview with a structured questionnaire. The results from spirometry and EIT test will be correlated and compared to identify the feasibility and accuracy of EIT lung device. Lung function parameters (e.g. FEV1, FVC, and FEV1/FVC ratio) measured using a spirometer would also be calculated from lung flow-volume curves derived from continuous EIT functional images. Regional lung function assessment will also be explored using EIT, and establish regional EIT features that could assist in screening and evaluating different chronic lung diseases. The EIT-derived indicators will be finally analyzed together with demographics, clinical assessments and patient history to derive fine grained insights and elucidate the effect of demographics and biometrics on EIT lung data. The parameters include, but not limited to, age, chest size, gender, weight, height, BMI, smoking habits and ethnicity. The analysis will improve the stability of the EIT indicators, and ultimately increase their predictive power towards diseased lung regions. With the availability of the EIT device on lung function assessment, which was validated with spirometry findings, patients who are unable to perform spirometry but need a proper lung function assessment can benefit by having the EIT test. These patients include but not limited to those who need major lung resection and interstitial lung diseases on anti-fibrotic. EIT can also be a more comfortable alternative to spirometry for patients who need lung function assessment.

Evaluation of serum KL6 level in rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

The aim of this study is to examine the peripheral muscle oxygenation of patients with Chronic Obstructive Pulmonary Disease at rest, during submaximal exercise and recovery, and to examine the effects of disease severity and respiratory functions on peripheral muscle oxygenations. In this study, the effect of disease severity and respiratory problems on peripheral muscle metabolism of patients with COPD will be explained.

The concerned patients are children and adults suffering from idiopathic interstitial pneumonias, other chronic fibrosing interstitial pneumonias with a progressive phenotype, and interstitial pneumonia associated with Scleroderma and related cases of patients carrying a mutation on one of the telomere-associated genes. This is a national, observational, longitudinal, multicenter study that will be conducted retrospectively and prospectively. It aims to collect consistent and comparable clinical data for patients and their relatives, whether they carry a mutation or not, affected by diffuse idiopathic interstitial pneumopathy. The expected duration of the study, including data analysis, is approximately 10 years (5 years for participant enrollment and 5 years of follow-up, in addition to the steps for data management and statistical analyses). Each participating center will inform every participant by providing an information sheet, and their written consent will be obtained before including them in the study and commencing data collection. Prospective medical data will be collected at 6 months to 1 year after enrollment and then at least once per year for patients up to 5 years and 5 years for their relatives. Participants will complete a self-questionnaire during their regular follow-up consultations or by accessing a secure interface.

Advancements in imaging capacities and the development of a precise puncture-guiding transducer have made transthoracic ultrasonography a useful diagnostic tool for evaluating peripheral subpleural lung tumours. Different human tissues have varying levels of elasticity because of the properties of the extracellular matrix. Pleural two-dimensional (2D) shear-wave elastography (SWE) can be used to differentiate between malignant pleural effusion and benign pleural disease. Transthoracic 2D-SWE uses acoustic radiation force and assesses the velocity of tissue displacement propagation in multiple focal zones. The shear waves are monitored in 2D by creating a near-cylindrical shear-wave cone, enabling measurement of the shear-wave speed or Young's modulus (E) on a colour quantitative elastogram. Based on the hypothesis that transthoracic 2D-SWE could add accurate tissue stiffness information to B-mode grayscale ultrasound images and help in differentiating lung malignancy from benign lung lesions.

Research on the impact of lung diseases on neuropsychological functioning has revealed impaired cognitive processing in patients with a variety of pulmonary disorders. While the mechanisms responsible for the association of pulmonary diseases and neurocognitive functioning remain unclear, some researchers have attributed it to reduced oxygenation of the brain. Early detection and accurate management of comorbidity have benefits in reducing ILD morbidity and mortality.

This research study is being conducted to evaluate the feasibility of using technology to deliver a remote home exercise program and assess the health outcomes of patients with chronic lung diseases. Specific objectives are to assess the interventions on patients: 1) Lung function, 2) Dyspnea, 3) Fatigue, 4) Exercise capacity, 5) Self-efficacy, and 6) Health-related quality of life. The investigators will also be evaluating the practicality of using videoconferencing and commercial wearable telemonitoring devices (ie. smart watches) for the implementation of the intervention in this group of patients.

Prospective observational study of hospitalised and non-hospitalised patients post- infection with SARS-CoV-2. The study aims to recruit 2000 individuals, with proven COVID-19, who were not hospitalised but presented to Long-COVID clinics with persistent respiratory symptoms such as breathlessness or cough and are referred for cross-sectional imaging (computer tomography, CT) at baseline (3 months weeks after their first COVID-19 symptoms). The study will run for 18 months.