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Assessment of breath volatile organic compounds in acute cardiorespiratory breathlessness: a protocol describing a prospective real-world observational study

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posted on 2019-03-26, 11:07 authored by Wadah Ibrahim, Michael Wilde, Rebecca Cordell, Dahlia Salman, Dorota RuszkiewiczDorota Ruszkiewicz, Luke Bryant, Matthew Richardson, Robert C. Free, Bo Zhao, Ahmed Yousuf, Christobelle White, Richard Russell, Sheila Jones, Bharti Patel, Asia Awal, Rachael Phillips, Graham Fowkes, Teresa McNally, Clare Foxon, Hetan Bhatt, Rosa Peltrini, Amisha Singapuri, Beverley Hargadon, Toru Suzuki, Leong L. Ng, Erol Gaillard, Caroline Beardsmore, Kimuli Ryanna, Hitesh Pandya, Tim Coates, Paul S. Monks, Neil Greening, Christopher E. Brightling, Paul Thomas, Salman Siddiqui
Introduction Patients presenting with acute undifferentiated breathlessness are commonly encountered in admissions units across the UK. Existing blood biomarkers have clinical utility in distinguishing patients with single organ pathologies but have poor discriminatory power in multifactorial presentations. Evaluation of volatile organic compounds (VOCs) in exhaled breath offers the potential to develop biomarkers of disease states that underpin acute cardiorespiratory breathlessness, owing to their proximity to the cardiorespiratory system. To date, there has been no systematic evaluation of VOC in acute cardiorespiratory breathlessness. The proposed study will seek to use both offline and online VOC technologies to evaluate the predictive value of VOC in identifying common conditions that present with acute cardiorespiratory breathlessness. Methods and analysis A prospective real-world observational study carried out across three acute admissions units within Leicestershire. Participants with self-reported acute breathlessness, with a confirmed primary diagnosis of either acute heart failure, community-acquired pneumonia and acute exacerbation of asthma or chronic obstructive pulmonary disease will be recruited within 24 hours of admission. Additionally, school-age children admitted with severe asthma will be evaluated. All participants will undergo breath sampling on admission and on recovery following discharge. A range of online technologies including: proton transfer reaction mass spectrometry, gas chromatography ion mobility spectrometry, atmospheric pressure chemical ionisation-mass spectrometry and offline technologies including gas chromatography mass spectroscopy and comprehensive two-dimensional gas chromatography-mass spectrometry will be used for VOC discovery and replication. For offline technologies, a standardised CE-marked breath sampling device (ReCIVA) will be used. All recruited participants will be characterised using existing blood biomarkers including C reactive protein, brain-derived natriuretic peptide, troponin-I and blood eosinophil levels and further evaluated using a range of standardised questionnaires, lung function testing, sputum cell counts and other diagnostic tests pertinent to acute disease. Ethics and dissemination The National Research Ethics Service Committee East Midlands has approved the study protocol (REC number: 16/LO/1747). Integrated Research Approval System (IRAS) 198921. Findings will be presented at academic conferences and published in peer-reviewed scientific journals. Dissemination will be facilitated via a partnership with the East Midlands Academic Health Sciences Network and via interaction with all UK-funded Medical Research Council and Engineering and Physical Sciences Research Council molecular pathology nodes. Trial registration number NCT03672994


This research was funded by the Medical Research Council (MRC), Engineering and Physical Sciences Research Council (EPSRC) Stratified Medicine Grant for Molecular Pathology Nodes (Grant No. MR/N005880/1) and Midlands Asthma and Allergy Research Association (MAARA), and carried out at the University Hospitals of Leicester NHS Trust and University of Leicester, supported by the NIHR Leicester Biomedical Research Centre and the NIHR Leicester Clinical Research Facility



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BMJ Open






IBRAHIM, W. ... et al., 2019. Assessment of breath volatile organic compounds in acute cardiorespiratory breathlessness: a protocol describing a prospective real-world observational study. BMJ Open, 9(3): e025486.


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