View clinical trials related to Aspergillosis.
Filter by:This study explores the role of treatment with interferon-gamma to improve outcomes in chronic pulmonary aspergillosis (CPA). CPA is a progressive infection caused by the fungus Aspergillus affecting patients with chronic lung disease like Chronic Obstructive Lung Disease (COPD) or previously treated tuberculosis (TB). It causes gradual destruction of lung tissue by slowly enlarging cavities, frequent secondary infections and poor quality of life. Because of its indolent nature and nonspecific x-ray findings, it often remains unrecognised for years. Around 3600 people live with CPA in the United Kingdom. Mortality from CPA may be up to 40% in five years. Treatment for CPA relies on antifungals for prolonged periods, but only around 60% of patients improve. It is often long-term or lifelong as the response is slow and some patients experience relapses. In addition, only one class of oral antifungal drugs is licensed for CPA, and they are associated with side effects and high cost. Better treatments are needed for CPA. We do not know why many patients do not respond to treatment. Maybe CPA patients have a weakened immune system and are more susceptible to Aspergillus. Our data suggest that CPA patients produce lower amounts of ΙFNγ, a substance that facilitates the immune system's response against Aspergillus. We have also shown that, when given to patients with CPA who have failed to improve on antifungal treatment, interferon-gamma leads to improvement in important patient-centred outcomes like flares of lung disease or hospital admissions. Interferon-gamma is already in use in the National Health Service of the United Kingdom for other indications. Therefore, its use in CPA should be explored. However, CPA is a rare condition and the tolerability of interferon-gamma is not fully established in these patients. To understand whether a large-scale study is feasible in CPA, we first need preliminary data in smaller numbers of patients. We propose a randomised trial of interferon-gamma in addition to antifungals in CPA. Patients with CPA starting antifungal treatment will be eligible. Participants (25 per group) will be randomly assigned to interferon-gamma for 12 weeks (in addition to antifungals) or antifungals only. To test whether the treatment works, we will use measurements of the cavities on chest CT scan and scores on a quality-of-life questionnaire. We will assess for tolerability of treatment at intervals similar to clinical practice. Criteria for progression to the large-scale study will be set based on the proportion of patients willing to participate, and on the proportion who complete the treatment. Data collected on those parameters will allow us to determine the number needed for a definite study. If the large-scale study confirms our observations that interferon-gamma improves outcomes in CPA, then treatment duration can be shortened and relapses avoided. In addition, interferon-gamma can then be explored in other chronic lung disease.
Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Allergic bronchopulmonary aspergillosis (ABPA) is a complex bronchopulmonary disease resulting from immunological reactions against Aspergillus Fumigatus. The development of a model of bronchial epithelium generated from patients with chronic lung disease will allow the modeling of bronchial tissue to understand the formation of these mucus plugs. This study aims to validate this model The investigators propose to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments: Differentiation of an Induced Pluripotent Stem cell (iPSC) clone derived from blood sample (Peripheral Blood Mononuclear Cells) of Type 2 inflammation (T2) severe asthma and Allergic Bronchopulmonary Aspergillosis (ABPA) in order to obtain differentiated bronchial epithelia in vitro.
Many children and young people are at risk of invasive fungal disease (IFD), such as those who have had a haematopoietic stem cell transplants, those with an immune deficiency or those who are prescribed immunosuppressive drugs, for example, corticosteroids. One type of mould that causes invasive fungal disease is called Aspergillus. There is currently no quick test which can tell us if someone has an invasive fungal disease caused by Aspergillus called Aspergillosis. It is a difficult condition to diagnose and the results from the tests that are involved take days or weeks to come back. These tests including a few different blood tests, a scan of the lungs (CT scans) and taking fluid from inside the lungs/airway. A new test for Aspergillosis is the lateral flow device (LFD) assay. This is a rapid test which gives a result within minutes. It involves testing a sample of the fluid from the lungs/airway. This fluid can be obtained as part of the routine investigations for Aspergillosis. It has been shown to be a good and safe test in adults but the investigators do not know if it will be a valuable test in children and young people yet. The purpose of this study is to determine whether the LFD test can effectively diagnose Aspergillosis in children and young people.
While ABPA and CPA represent two distinct manifestations of Aspergillus-related lung disease, there is an overlap of investigations that are currently used for the diagnosis of these entities. In a previous study, the authors have demonstrated that 22% of subjects with CPA fulfilled the obligatory criteria for ABPA. While the preferable therapy in patients with ABPA is systemic glucocorticoids, the primary therapy in CPA is oral triazoles. However, a different management protocol in the "overlap group" with low doses of glucocorticoids and triazoles, needs to be systematically explored. In this study the investigators intend to compare the clinical outcomes in subjects with ABPA-CPA overlap treated either with oral azoles or a combination of systemic glucocorticoids and oral azoles.
To assess the safety and efficacy of nebulized PC945 in combination with systemic antifungal therapy for the treatment of refractory IPA
Invasive aspergillosis (IA) are difficult to diagnose in the ICU population, as the patients often do not present the conventional risks factors of immunocompromised patients (EORTC/MSG criteria). In the ICU population, patients often present other risk factors, such as cirrhosis, COPD, influenza and currently SARS-Cov2. The clinicians are thus currently missing precise criteria to distinguish colonization from IA in these patients, while they need to decide if an antifungal treatment is necessary or not. A new algorithm, entitled BM ASP ICU, based on investigators field experience and the scientific literature, which takes into account both EORTC/MSG criteria and a combination of fungal biomarkers, was proposed recently by Haman et al, Annals Intensive Care, 2021. Additional serological assays (immunoprecipitation and ELISA) showed since their interest, especially concerning SARS-Cov2 patients, a new population at risk of IA in the ICU, which emerged in the past months. The present study aims at prospectively implementing the BM ASP ICU algorithm during two years in the routine practice of six ICU units distributed in general and teaching hospitals situated northeast of France. The BM ASP ICU algorithm would be completed by serological assays aiming at assessing a sensitization towards Aspergillus fumigatus. The investigators plan to include 400 ICU patients at risk of IA; SARS-Cov2 patients will be part of the cohort. A weekly screening including culture of respiratory samples, galactomannan antigen, fungal qPCRS (targeting A. fumigatus), and A. fumigatus serology will be applied for all included patients. The performance (sensitivity and specificity, likelihood ratios) of each fungal biomarkers, alone and in combination with others, will be assessed, for all patients, and also within subgroups of patients with specific risk factors (such as SARS-Cov2 for example). These results should lead to solid understanding of which combination of tests is optimal to diagnose IA and thus to initiate appropriate antifungal treatment. the investigators hope that this study will result in improved survival rate of ICU patients with IA.
This study is being done to evaluate the efficacy of treatment using oral glucocorticoid, anti-fungal agent, anti-IgE mAb for patient with ABPA.
The purpose of this study is to compare treatment with olorofim versus treatment with AmBisome® followed by standard of care (SOC) in patients with IFD caused by proven IA or probable lower respiratory tract disease Aspergillus species (invasive aspergillosis, IA).
COVID-19 associated pulmonary aspergillosis (CAPA) is considered a potentially life-threatening infection in critically ill COVID (Corona Virus disease)-19 patients. This study will investigate the efficacy of mold-active prophylaxis with posaconazole for patients with severe SARS (severe acute respiratory syndrome)-CoV-2 infection admitted to the ICU (intensive care unit) in a multi-center case-control study in Europe.
At present, pulmonary diffusion and target antifungal concentrations for APC in patients with sarcoidosis or chronic obstructive pulmonary disease (COPD) are unknown.