Skip to main content
OpenTrials
Completed

NCT Number: NCT03672994

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Asthma Breathlessness Bronchial Diseases COPD Cardiovascular Diseases Chronic Disease Community-Acquired Infections Community-Acquired Pneumonia Disease Attributes Dyspnea Healthy Heart Diseases Heart Failure Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Infections Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pulmonary Disease, Chronic Obstructive Respiration Disorders Respiratory Hypersensitivity Respiratory Tract Diseases Respiratory Tract Infections Signs and Symptoms Signs and Symptoms, Respiratory

Age range

5 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

NIHR Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital

Leicester, Leicestershire, LE3 9QP, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Discovery of exhaled breath biomarkers

    Time frame: 0-6 months

    To evaluate the sensitivity, specificity, positive and negative predictive value of metabolomic biomarkers in exhaled breath samples to identify acute breathlessness, defined as one or more of (i) patient defined acute breathlessness and/or a (ii) 1 unit increase in Extended Medical Research Council breathlessness score (eMRC)

Secondary outcomes

  1. Patient defined breathlessness

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Participants are asked to provide information on their state of breathlessness

  2. COPD Assessment Test (CAT) (Questionnaire)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Evaluation and rehabilitation education guidance on the respiratory and motor functions of patients with chronic obstructive pulmonary disease. The CAT has a scoring range of 0-40, with Since COPD is a progressive disease, a fi xed target score for all patients cannot be set. In Practice, a target for improvement in individual patient CAT scores may be set, based on an holistic assessment of the patient. A change of 2 units suggests a meaningful difference. This test should be used in conjunction with the eMRC and forced expiratory volume in one second (FEV1) to determine COPD health assessment of participants.

  3. NASA task load index

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Evaluation breath testing work load using mental, physical, temporal, performance, effort and frustration. Participants are asked to mark a scale based on how demanding the task was for each of the domains above.

  4. Asthma quality of life questionaire (AQLQ)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Evaluation quality of life in asthmatic patients based on their level of activity, symptoms, environment and emotion.

  5. Asthma control questionnaire (ACQ)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Measure of asthma control

  6. extended Medical Research Council (eMRC) Dyspnea Scale

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Assessing respiratory breathlessness symptoms (Grade 0-5b, with Grade 0 being breathlessness with strenuous exercise to Grade 5b being breathlessness for daily activities like dressing).

  7. Visual analogue score (VAS) total and individual dyspnoea, cough and wheeze (100mm) scores

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    The participant is asked to place a mark (X) on the scale at the point that best describes their health currently. Minimum score 0mm (better outcome), maximum score 100mm (worse outcome) for each section of the scale (dyspnoea, cough, wheeze).

  8. NewYork Heart Association Dyspnoea score (NYHA)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Assessing grades of breathlessness specifically designed for heart failure patients

  9. Sputum collection for assessment of purulence, cytology and metagenomics

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Participants are asked to provide a spontaneous sputum sample assessing purulence, cytology and metagenomics

  10. Pre and post bronchodilator (BD) spirometry to assess lung function

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    To assess lung function

  11. fraction exhaled nitric oxide (FeNO) assessing airway inflammation

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    To assess airway inflammation in asthmatics. Patients are asked to blow into a mouthpiece for few seconds which detects the amount of exhaled nitric oxide.

  12. Hand held oscillometry assessing small airway lung function

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    To assess small airway lung function

  13. Quadriceps ultrasound measuring quadriceps size as a degree of frailty

    Time frame: visit 1a (first visit)

    To assess degree of frailty and muscle breakdown during hospital admission. Participants have their quadriceps muscle size measured using an ultrasound machine.

  14. Four meter gait

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    physical performance - measure of frailty

  15. Exacerbation history

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    participants are asked to provide information on recent exacerbations of airway disease

  16. DECAF score assessing in hospital mortality in COPD patients

    Time frame: visit 1a (first visit)

    DECAF score has a minimum score of 1 (better outcome) and a maximum score of 6(worse outcome) used for assessment of severity of COPD exacerbation measures eMRC score, Eosinopenia, consolidation, acidemia and atrial fibrillation

  17. CURB65 score assessing mortality in Pneumonia patients

    Time frame: visit 1a (first visit)

    CURB65 is used in assessment of 30 day mortality of Pneumonia based on confusion, urea, respiratory rate, blood pressure and age.Scores range from 1 (better outcome) to 5 (worse outcome)

  18. BTS asthma severity score

    Time frame: visit 1a (first visit)

    BTS asthma severity score is used in assessment of asthma severity based on peak flow, respiratory rate, oxygen levels, altered level of consciousness, arrythmia, hypotension, cyanosis, silent chest and respiratory effort. Patients are then classified into mild (better outcome), moderate, severe and life threatening (worse outcome).

  19. Meta analysis global group in chronic heart failure (MAGGIC - risk calculator)

    Time frame: visit 1a (first visit)

    Assessment of heart failure severity based on age, gender, diabetes, COPD, heart failure diagnosed in the last 18 months, current smoker, NYHA class, b blockers, ACEI or ARB, BMI, systolic BP, creatinine and ejection fraction

  20. Sputum differential Cell Count

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Differential Cell Count to assess inflammation at exacerbation events.

  21. Breath volatile organic compound (VOC) profiling

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Participants are asked to provide a breath sample to measure VOC using Compact Mass Spectrometer (CMS), Gas chromatography ion mobility spectrometer (GC-IMS), gas chromatography mass spectrometer (GC-MS), Proton transfer reaction time of flight mass spectrometer (PTR-Tof-MS), gas chromatography gas chromatography mass spectrometer (GCxGC-MS).

  22. Serum/Plasma Inflammatory Biomarkers

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    To assess systemic inflammation. Plasma/ serum biomarkers are exploratory and we do not have a specific list of biomarkers yet.

  23. Full blood count (FBC)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Blood Biochemistry

  24. C-reactive protein (CRP)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Blood Biochemistry

  25. Troponin-I

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Blood Biochemistry

  26. B-type naturitic peptide (BNP)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Blood biochemistry

  27. RNA (PAXgene)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Blood Biochemistry

  28. DNA (PAXgene)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Blood Biochemistry

  29. Age

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Demographics

  30. Smoking status, calculated using pack years (no. of cigarettes smoked per day X no. of years smoked divided by 20

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Demographics

  31. BMI in kg/m^2

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Demographics

  32. Gender

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Demographics

  33. Heart rate

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Vital signs

  34. Blood pressure

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Vital signs

  35. Oxygen saturations

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Vital signs

  36. Temperature

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Vital signs

  37. Medical history

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    medical history

  38. Current medications

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Medical history

  39. Physical examination

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Physical examination

  40. 12 lead Electrocardiogram (ECG)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    cardiac function

  41. Echocardiogram (ECHO)

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    cardiac function

  42. Chest Xray

    Time frame: visit 1a

    Respiratory function

  43. Height

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Demographics

  44. Weight

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Demographics

  45. Ethnicity

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Demographics

  46. Review of adverse events and serious adverse events

    Time frame: visit 1a (first visit), visit 2 (0-6 months)

    Review of untoward medical occurrences

Sponsors and collaborators

Lead sponsor

University of Leicester

Other

Collaborators

  • Advion Biosciences Ltd
  • B & S ANALYTIK GmbH
  • Engineering and Physical Sciences Research Council, UK
  • Loughborough University
  • Medical Research Council
  • Owlstone Ltd
  • University Hospitals, Leicester

Registry information

Acronym: EMBER

Important dates

Study start
2017
Primary completion
2018
Study completion
2019
First posted
Sep 17, 2018
Registry last updated
Jan 30, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.