Browsing by Author "Brinkman P."

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    Breath metabolomics for diagnosis of acute respiratory distress syndrome
    (2024-12-01) Zhang S.; Hagens L.A.; Heijnen N.F.L.; Smit M.R.; Brinkman P.; Fenn D.; van der Poll T.; Schultz M.J.; Bergmans D.C.J.J.; Schnabel R.M.; Bos L.D.J.; Zhang S.; Mahidol University
    Background: Acute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation. Aim: To evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients. Methods: This two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC–MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into “certain ARDS”, “certain no ARDS” and “uncertain ARDS” groups. The patients with “certain” labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS). Results: A total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63–0.78) in the derivation cohort and 0.63 (CI 0.52–0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance. Conclusion: An exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.
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    Microbial Volatiles as Diagnostic Biomarkers of Bacterial Lung Infection in Mechanically Ventilated Patients
    (2023-03-15) Ahmed W.M.; Fenn D.; White I.R.; Dixon B.; Nijsen T.M.E.; Knobel H.H.; Brinkman P.; Van Oort P.M.P.; Schultz M.J.; Dark P.; Goodacre R.; Felton T.; Bos L.D.J.; Fowler S.J.; Ahmed W.M.; Raventos A.A.; Bannard-Smith J.; Bos L.D.J.; Camprubi M.; Coelho L.; Davie A.; Diaz E.; Goma G.; Felton T.; Fowler S.J.; Goodacre R.; Johnson C.; Knobel H.H.; Lawal O.; Leopold J.H.; Martin-Loeches I.; Nijsen T.M.E.; Van Oort P.M.P.; Povoa P.; Rattray N.J.W.; Rijnders G.; Schultz M.J.; Steenwelle R.; Sterk P.J.; Valles J.; Verhoeckx F.; Vink A.; Weda H.; Winters T.; Zakharkina T.; Mahidol University
    Background: Early and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as noninvasive biomarkers of infection to support clinical diagnosis. Methods: In this study, we investigated the diagnostic potential of in vitro-confirmed mVOCs in the exhaled breath of patients under mechanical ventilation from the BreathDx study. Samples were analyzed by thermal desorption-gas chromatography-mass spectrometry. Results: Pathogens from bronchoalveolar lavage (BAL) cultures were identified in 45 of 89 patients and Staphylococcus aureus was the most commonly identified pathogen (n = 15). Of 19 mVOCs detected in the in vitro culture headspace of 4 common respiratory pathogens (S. aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli), 14 were found in exhaled breath samples. Higher concentrations of 2 mVOCs were found in the exhaled breath of patients infected with S. aureus compared to those without (3-methylbutanal: P <. 01, area under the receiver operating characteristic curve [AUROC] = 0.81-0.87; and 3-methylbutanoic acid: P =. 01, AUROC = 0.79-0.80). In addition, bacteria identified from BAL cultures that are known to metabolize tryptophan (E. coli, Klebsiella oxytoca, and Haemophilus influenzae) were grouped and found to produce higher concentrations of indole compared to breath samples with culture-negative (P =. 034) and other pathogen-positive (P =. 049) samples. Conclusions: This study demonstrates the capability of using mVOCs to detect the presence of specific pathogen groups with potential to support clinical diagnosis. Although not all mVOCs were found in patient samples within this small pilot study, further targeted and qualitative investigation is warranted using multicenter clinical studies.
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    Octane in exhaled breath to diagnose acute respiratory distress syndrome in invasively ventilated intensive care unit patients
    (2023-09-01) Hagens L.A.; Heijnen N.F.L.; Smit M.R.; Verschueren A.R.M.; Nijsen T.M.E.; Geven I.; Presură C.N.; Rietman R.; Fenn D.W.; Brinkman P.; Schultz M.J.; Bergmans D.C.J.J.; Schnabel R.M.; Bos L.D.J.; Hagens L.A.; Mahidol University
    Background The concentration of exhaled octane has been postulated as a reliable biomarker for acute respiratory distress syndrome (ARDS) using metabolomics analysis with gas chromatography and mass spectrometry (GC-MS). A point-of-care (POC) breath test was developed in recent years to accurately measure octane at the bedside. The aim of the present study was to validate the diagnostic accuracy of exhaled octane for ARDS using a POC breath test in invasively ventilated intensive care unit (ICU) patients. Methods This was an observational cohort study of consecutive patients receiving invasive ventilation for at least 24 h, recruited in two university ICUs. GC-MS and POC breath tests were used to quantify the exhaled octane concentration. ARDS was assessed by three experts following the Berlin definition and used as the reference standard. The area under the receiver operating characteristic curve (AUC) was used to assess diagnostic accuracy. Results 519 patients were included and 190 (37%) fulfilled the criteria for ARDS. The median (interquartile range) concentration of octane using the POC breath test was not significantly different between patients with ARDS (0.14 (0.05–0.37) ppb) and without ARDS (0.11 (0.06–0.26) ppb; p=0.64). The AUC for ARDS based on the octane concentration in exhaled breath using the POC breath test was 0.52 (95% CI 0.46–0.57). Analysis of exhaled octane with GC-MS showed similar results. Conclusions Octane in exhaled breath has insufficient diagnostic accuracy for ARDS. This disqualifies the use of octane as a biomarker in the diagnosis of ARDS and challenges most of the research performed up to now in the field of exhaled breath metabolomics.