View clinical trials related to Pulmonary Aspergillosis.
Filter by:The treatment of CPA is with oral itraconazole for 6-12 months. Oral itraconazole results in better clinical outcomes in CPA compared to supportive care. A recent study comparing 6 months with 12 months of oral itraconazole for longer duration treatment found longer duration reduced CPA relapse and improved clinical outcomes. However, longer duration of itraconazole could cause emergence of drug resistant Aspergillus fumigatus and therapy related adverse event. A recent study found nebulized amphotericin B non-inferior to oral itraconazole for treating CPA as primary therapy. However, the study was small and included patients with simple aspergilloma and used nebulized amphotericin B for 7 days.To be effective, an inhaled drug should be delivered in sufficient quantity to achieve therapeutic levels.The minimum inhibitory concentration of amphotericin B for A.fumigatus is 0.5 mg/L. In one study, nebulization of 30 mg of amphotericin B deoxycholate achieved a mean concentration of 0.68 mg/L in the bronchoalveolar lavage fluid. Notably, the serum levels of amphotericin B after nebulization are 20 times less than after systemic administration and is safer. Further, there is a dose-response relation with nebulized amphotericin B, the higher the dose used for nebulization, the higher are the levels achieved in the lung tissue. Nebulized amphotericin B has been used in lung transplant recipients to prevent invasive aspergillosis. Also, two recent studies have demonstrated that use of nebulized amphotericin B as maintenance therapy led to a reduction in ABPA relapse rates and prolonged time to exacerbation. We believe that inhaled amphotericin B as a maintenance therapy could reduce CPA relapse and prolong time to relapse. In this study, we plan to evaluate nebulized amphotericin B as a maintenance therapy in clinically stable CPA patients treated with 12 months of oral antifungal therapy
The investigators hypothesize that a combination of prednisolone and itraconazole would significantly reduce the exacerbation rate at one-year of patients with acute allergic bronchopulmonary aspergillosis (ABPA) compared to itraconazole or prednisolone monotherapy. In this study, 300 subjects aged ≥18 years with acute ABPA will be randomized to treatment with either prednisolone, itraconazole, or prednisolone plus itraconazole, all for four months each. After collecting baseline demographic, immunologic, and imaging data, the investigators will follow the patients every 2 months for the first two visits and then every four months for three visits. The primary outcome will be the proportion of subjects experiencing exacerbation (asthma or ABPA) 12 months after treatment completion.
The diagnosis of invasive pulmonary aspergillosis (IPA) bears grave implications for the prognosis and treatment plan of the immunosuppressed patient. Thus far, such diagnosis in the immunosuppressed patient, such as patients with acute myeloid leukemia (AML), relied heavily on chest computed tomography (CT) and bronchoalveolar lavage (BAL), an invasive approach bearing many caveats. Volatile organic compounds (VOC) are compounds that could be detected in exhaled air, and have shown some potential in the non-invasive diagnosis of various conditions, including IPA. In this prospective longitudinal study we aim to compare the VOC profiles of patients diagnosed with AML (baseline) to the profile of the same patient diagnosed with IPA later on, and to the post recovery profile in the same patient. This approach should resolve many of the issues plaguing prior attempts at VOC based IPA diagnosis, mainly the lack of properly designed controls. Samples will be collected from consenting patients using Tedlar bags, and analyzed using thermal desorption gas chromatography mass spectrometry (TD-GC-MS). VOCs detected will be digitally analyzed to construct different classification models, with predictive performances compared to the clinical diagnosis using the accepted methods will be assessed by binary logistic regression.
The last decade has seen a significant increase in secondary Aspergillus infections, not only due to primary hypersensitivity, and immunodeficiency based on oncological diseases and their therapy, but mainly due to a rise in severe respiratory infections (H1N1, COVID-19, bacterial infections). This is most evident in critically ill patients whose life is threatened by invasive pulmonary aspergillosis (IPA), with over 90 % of cases being caused by Aspergillus fumigatus. In recent decades, various biomarkers with well-known limits of use (Aspergillus DNA, galactomannan, 1,3-ß-D-glucan) have been used for early diagnosis of IPA. However, the clinical need to clearly distinguish the onset of IPA from colonization is much more significant. The current biomarkers only provide "probable IPA" interpretation, and the diagnosis is rarely confirmed. Based on our preliminary studies, the use of new low molecular weight substances (secondary metabolites) combined with acute-phase proteins (pentraxin 3) allows very reliable immediate confirmation of IPA. In tissue samples, bronchoalveolar lavage fluid, endotracheal aspirate, breath condensate, serum, and urine of critically ill patients, the investigators will be able to recognize and confirm IPA in time using highly sensitive mass spectrometry detecting specific microbial siderophores in correlation with a significantly increased concentration of acute-phase host protein (pentraxin 3) within hours of the beginning of the invasion of lung tissue. Through a prospective multicentre study, the investigators will evaluate the benefit of new biomarkers in non-invasive IPA confirmation, improve the IPA diagnostic algorithm and transfer the detection method to MALDI-TOF spectrometers widely used in Clinical laboratories in the Czech Republic. In MALDI-TOF mass spectrometry, the ion source is matrix-assisted laser desorption/ionization (MALDI), and the mass analyser is a time-of-flight (TOF) analyser. The study results will contribute to a high clarity of IPA cases, the accurate introduction of antifungal therapy, and a better prognosis of survival of critically ill patients.
The prevalence of ascariasis in COPD patients with and without concomitant pulmonary aspergillosis and in controls will be determined. To assess the influence of ascaridosis on the development of pulmonary aspergillosis in COPD patients cytokine status of patients will be studied.
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.
At present, pulmonary diffusion and target antifungal concentrations for APC in patients with sarcoidosis or chronic obstructive pulmonary disease (COPD) are unknown.