View clinical trials related to Pulmonary Aspergillosis.
Filter by:This is a single center open-label feasibility trial involving a single study visit for participants. The purpose of the study is to demonstrate the feasibility of [68Ga]Ga-DFO-B PET/CT (gallium-68-deferoxamine) for the visualization of pulmonary Aspergillus infection. The incidence of fungal infections is on the rise and are associated with significant mortality. Diagnosis pulmonary aspergillosis can be can be challenging, often requiring invasive tests such as bronchoscopy and lung tissue biopsies. Molecular imaging, specifically using radiolabeled siderophores like [68Ga]Ga-DFO-B, offers a non-invasive and location-specific approach to visualize and evaluate infections. Siderophores, critical for pathogenic microbes like Aspergillus fumigatus, play a role in iron acquisition. Preclinical studies with radiolabeled deferoxamine (DFO-B) demonstrated distinct accumulation at infection sites. Additionally, [68Ga]Ga-DFO-B PET/CT may differentiate between Aspergillus infection and cancer, making it a promising non-invasive diagnostic tool for pulmonary aspergillosis.
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.
This prescreening study is being conducted to diagnose ABPA in selected patients with asthma and to increase the potential number of eligible participants for the ongoing Study 601-0018 of PUR1900 in subjects with ABPA. See: NCT05667662. Additionally, this prescreening study may provide information that could assist the conduct of future studies conducted by Pulmatrix.
Voriconazole Inhalation Powder is available on an expanded access basis to patients with pulmonary aspergillosis for up to 12 weeks. Duration of treatment may be extended on a case-by-case basis depending on drug availability and after discussion with the Sponsor.
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.
Mechanically ventilated patients are at risk of developing ventilator-associated pneumonia (VAP). Invasive pulmonary aspergillosis (IPA), the diagnosis of which motivates the implementation of specific treatments, is one of the causes of VAP. The hypothesis of the study is that the incidence of IPA is 12.4%. For each patient presenting with a suspicion of VAP and requiring a bronchoalveolar lavage (BAL), the diagnosis of API will be evaluated by biological examinations performed on blood and BAL. Medical and surgical history as well as clinical and biological data will be collected for 28 days or until discharge from the ICU.
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.