Exhaled Breath Metabolomic Biomarkers in the Acutely Breathless Patient
Exhaled Breath Metabolomic Biomarkers in the Acutely Breathless Patient
An acute study carried out across three acute admissions units within Leicestershire. The
 study is aimed at discovery and validation of volatile organic compounds (VOCs) in exhaled
 breath. Participants will be recruited and tested within 24 hours of admission and once
 recovered, up to 6 months following discharge.
A prospective real world observational study carried out across three acute admissions units.
 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
 COPD will be recruited within 24 hours of admission. These will be matched to healthy
 volunteers from a similar environment. Additionally, school age children admitted with severe
 asthma will be evaluated and breath samples will be collected. All participants will undergo
 breath sampling on admission and upon recovery, up to six months following discharge. A range
 of online technologies including: proton-transfer-reaction mass spectrometry (PTR-MS), gas
 chromatography ion mobility spectrometry (GC-IMS), atmospheric pressure chemical ionisation-
 mass spectrometry (APCI-MS) and offline technologies including gas chromatography mass
 spectroscopy (GC-MS) and comprehensive two-dimensional gas chromatography-mass spectrometry
 (GCxGC-MS) will be utilised 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 (CRP), brain derived natriuretic peptide (BNP), Troponin-I and blood eosinophil
 levels and further evaluated using a range of standardised questionnaires, lung function
 testing including hand held forced oscillation technique (FOT) and fractional exhaled nitric
 oxide (FeNO), sputum cell counts and echocardiography for heart failure and COPD patients.
 Additional samples will be collected for bio-banking including urine, serum, plasma and
 sputum supernatants and plugs.
Inclusion Criteria:

 (i) Able to give informed consent for participation in the study. (ii) Male or Female, aged
 16 years or above (adult cohort) and 5-15 years for paediatric patients attending the acute
 care paediatric pathway.

 (iii) Capable (in the opinion of the EMBER clinical research investigator(s) of providing
 serial breath samples.

 (iv) Diagnosed with acute breathlessness as one of the primary indicator reasons by the
 clinical acute care team. This is not a requirement for healthy subjects or matched
 controls.

 (v) One of the indicator provisional diagnoses identified in section 7.1 following senior
 review by the clinical acute care team. This is not a requirement for healthy subjects or
 matched controls (vi) Able (in the Investigators opinion) and willing to comply with all
 study requirements.

 (vii) Willing to allow his or her General Practitioner and consultant, if appropriate, to
 be notified of participation in the study.

 (viii) Ability to understand English.

 Exclusion Criteria:

 (i) Female participants who are known to be pregnant, lactating or planning pregnancy
 during the course of the study.

 (ii) Current participation in a clinical trial of an investigative medicinal product or
 within 3 months or 5.5 half-lives of the IMP whichever is longer.

 (iii) Active or clinically suspected pulmonary tuberculosis (iv) In the opinion of the
 treating physician, breath sampling during the acute admission would be clinically unsafe
 or inappropriate due to the patient's condition or poor prognosis. Examples include
 malignancy or autoimmune disease with anticipated survival of under 1 year, and chronic
 renal replacement therapy.

 (v) Unable or unwilling to give informed consent by visit 1b. (vi) Any other significant
 disease or disorder which, in the opinion of the Investigator, may either put the
 participants at risk because of participation in the study, or may influence the result of
 the study, or the participant's ability to participate in the study.