Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry.

Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a reference strain were cultured while conidiation was prevented. Headspace samples were analyzed using a standardized method. Breath samples of patients from which the cultures were obtained were checked for the presence of the VOCs found in vitro. Each Aspergillus isolate produced a distinct VOC profile. These profiles could not be confirmed in exhaled breath in vivo.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma.

BACKGROUND: Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. OBJECTIVES: To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography/mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma. METHODS: Twenty-three patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analysed by GC/MS and eNose. Univariate analysis of covariance (ANCOVA), followed by multivariate principal component analysis (PCA) was used to reduce data dimensionality. Next paired t tests were utilized to analyse within-subject breath profile differences at the different time-points. Finally, associations between exhaled metabolites and sputum inflammation markers were examined. RESULTS: Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs loss of control and 86% (19/22) for loss of control vs recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs loss of control and loss of control vs recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥.46, P<.01). CONCLUSIONS & CLINICAL RELEVANCE: Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers was associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

Data management in multi-center clinical trials and the role of a nation-wide computer network. A 5 year evaluation.

Multidisciplinary collaboration in multi-center trials needs a formalized data management structure to ensure true progress monitoring and high quality research data. Cadans, a customized facility for data management, related to the Interuniversity Cardiology Institute of the Netherlands, designed a computer-based data management system for multidisciplinary multi-center collaborative research projects. In this paper we describe the system and the role of integrated access to research databases on a data network. Areas of concern are also discussed.