Exhaled Breath Metabolomic Biomarkers in the Acutely Breathless Patient
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 650
- 试验地点
- 1
- 主要终点
- Discovery of exhaled breath biomarkers
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(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.
排除标准
- •(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.
结局指标
主要结局
Discovery of exhaled breath biomarkers
时间窗: 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)
次要结局
- COPD Assessment Test (CAT) (Questionnaire)(visit 1a (first visit), visit 2 (0-6 months))
- Smoking status, calculated using pack years (no. of cigarettes smoked per day X no. of years smoked divided by 20(visit 1a (first visit), visit 2 (0-6 months))
- Serum/Plasma Inflammatory Biomarkers(visit 1a (first visit), visit 2 (0-6 months))
- Full blood count (FBC)(visit 1a (first visit), visit 2 (0-6 months))
- NewYork Heart Association Dyspnoea score (NYHA)(visit 1a (first visit), visit 2 (0-6 months))
- NASA task load index(visit 1a (first visit), visit 2 (0-6 months))
- Asthma quality of life questionaire (AQLQ)(visit 1a (first visit), visit 2 (0-6 months))
- Sputum collection for assessment of purulence, cytology and metagenomics(visit 1a (first visit), visit 2 (0-6 months))
- Four meter gait(visit 1a (first visit), visit 2 (0-6 months))
- DECAF score assessing in hospital mortality in COPD patients(visit 1a (first visit))
- BTS asthma severity score(visit 1a (first visit))
- C-reactive protein (CRP)(visit 1a (first visit), visit 2 (0-6 months))
- B-type naturitic peptide (BNP)(visit 1a (first visit), visit 2 (0-6 months))
- RNA (PAXgene)(visit 1a (first visit), visit 2 (0-6 months))
- Physical examination(visit 1a (first visit), visit 2 (0-6 months))
- extended Medical Research Council (eMRC) Dyspnea Scale(visit 1a (first visit), visit 2 (0-6 months))
- Pre and post bronchodilator (BD) spirometry to assess lung function(visit 1a (first visit), visit 2 (0-6 months))
- CURB65 score assessing mortality in Pneumonia patients(visit 1a (first visit))
- Troponin-I(visit 1a (first visit), visit 2 (0-6 months))
- Age(visit 1a (first visit), visit 2 (0-6 months))
- Heart rate(visit 1a (first visit), visit 2 (0-6 months))
- Blood pressure(visit 1a (first visit), visit 2 (0-6 months))
- Patient defined breathlessness(visit 1a (first visit), visit 2 (0-6 months))
- Asthma control questionnaire (ACQ)(visit 1a (first visit), visit 2 (0-6 months))
- Visual analogue score (VAS) total and individual dyspnoea, cough and wheeze (100mm) scores(visit 1a (first visit), visit 2 (0-6 months))
- Hand held oscillometry assessing small airway lung function(visit 1a (first visit), visit 2 (0-6 months))
- Gender(visit 1a (first visit), visit 2 (0-6 months))
- fraction exhaled nitric oxide (FeNO) assessing airway inflammation(visit 1a (first visit), visit 2 (0-6 months))
- Quadriceps ultrasound measuring quadriceps size as a degree of frailty(visit 1a (first visit))
- Exacerbation history(visit 1a (first visit), visit 2 (0-6 months))
- Meta analysis global group in chronic heart failure (MAGGIC - risk calculator)(visit 1a (first visit))
- Sputum differential Cell Count(visit 1a (first visit), visit 2 (0-6 months))
- Breath volatile organic compound (VOC) profiling(visit 1a (first visit), visit 2 (0-6 months))
- DNA (PAXgene)(visit 1a (first visit), visit 2 (0-6 months))
- BMI in kg/m^2(visit 1a (first visit), visit 2 (0-6 months))
- Medical history(visit 1a (first visit), visit 2 (0-6 months))
- Echocardiogram (ECHO)(visit 1a (first visit), visit 2 (0-6 months))
- Oxygen saturations(visit 1a (first visit), visit 2 (0-6 months))
- Temperature(visit 1a (first visit), visit 2 (0-6 months))
- Current medications(visit 1a (first visit), visit 2 (0-6 months))
- Height(visit 1a (first visit), visit 2 (0-6 months))
- Ethnicity(visit 1a (first visit), visit 2 (0-6 months))
- Review of adverse events and serious adverse events(visit 1a (first visit), visit 2 (0-6 months))
- 12 lead Electrocardiogram (ECG)(visit 1a (first visit), visit 2 (0-6 months))
- Chest Xray(visit 1a)
- Weight(visit 1a (first visit), visit 2 (0-6 months))