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

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 NCT0367299

Spirometry and FeNO testing for asthma in children in UK primary care: a prospective observational cohort study of feasibility and acceptability.

BACKGROUND:The National Institute for Health and Care Excellence recommends the use of spirometry and measuring the fraction of exhaled nitric oxide (FeNO) as part of the diagnostic work-up for children with suspected asthma, and spirometry for asthma monitoring, across all care settings. However, the feasibility and acceptability of these tests within primary care are not known. AIM:To investigate the feasibility, acceptability, training, and capacity requirements of performing spirometry and FeNO testing in children managed for asthma in UK primary care. DESIGN AND SETTING:Prospective observational study involving 10 general practices in the East Midlands, UK, and 612 children between 2016 and 2017. METHOD:Training and support to perform spirometry and FeNO in children aged 5 to 16 years were provided to participating practices. Children on the practice's asthma registers, and those with suspected asthma, were invited for a routine asthma review. Time for general practice staff to achieve competencies in performing and/or interpreting both tests, time to perform the tests, number of children able to perform the tests, and feedback on acceptability were recorded. RESULTS:A total of 27 general practice staff were trained in a mean time of 10.3 (standard deviation 2.7) hours. Usable spirometry and FeNO results were obtained in 575 (94%) and 472 (77%) children respectively. Spirometry is achievable in the majority of children aged ≥5 years, and FeNO in children aged ≥7 years. All of the staff and 97% of families surveyed provided positive feedback for the tests. CONCLUSION:After training, general practice staff obtained quality spirometry and FeNO data from most children tested. Testing was acceptable to staff and families. The majority of general practice staff reported that spirometry helped them to manage children's asthma better

Use of the ReCIVA device in breath sampling of patients with acute breathlessness: a feasibility study

Introduction: Investigating acute multifactorial undifferentiated breathlessness and understanding the driving inflammatory processes can be technically challenging in both adults and children. Being able to validate non-invasive methods such as breath analysis would be a huge clinical advance. The ReCIVA ® device allows breath samples to be collected directly onto sorbent tubes at the bedside for analysis of exhaled volatile organic compounds (eVOCs). We aimed to assess the feasibility of using this device in acutely breathless patients. Methods: Adults hospitalised with acute breathlessness and children aged 5-16 years with acute asthma or chronic stable asthma as well as healthy adult and child volunteers were recruited. Breath samples were collected onto sorbent tubes using the ReCIVA® device and sent for analysis by means of two dimensional gas chromatography-mass spectrometry (GCxGC-MS). The NASA Task Load Index (NASA-TLX) was used to assess the perceived task workload of undertaking sampling from the patients’ perspective. Results: Data was available for 65 adults and 61 children recruited. In total, 98.4% of adults and 75.4% of children were able to provide the full target breath sample using the ReCIVA ® device. NASA TLX measurements was available in the adult population with mean values of 3.37 for effort, 2.34 for frustration, 3.8 for mental demand, 2.8 for performance, 3.9 for physical demand and 2.8 for temporal demand. Discussion: This feasibility study demonstrates it is possible and acceptable to collect breath samples from both adults and children at the bedside for breathomics analysis using the ReCIVA® device

Group characteristics and spirometry results (based on GLI-White equations) according to centre.

<p>Group characteristics and spirometry results (based on GLI-White equations) according to centre.</p

Distribution of lung function data (based on GLI-White) vs. age according to centre.

<p><i>Symbols</i>: <i>Blue denotes data from boys and Red denotes data from girls</i>. <i>Dashed line = mean value and dotted lines 95% limits of agreement (Mean ± 2 SD) for each dataset</i>. Centres: A = Bangalore; B = Delhi; C = Gujarat; D = Hyderabad; E = CHASE (London); F = DASH (London); G = Leicester City; H = LRC (Leicester); I = SLIC (London). Note the different scales used on the y-axis reflecting the greater spread of FVC than FEV₁ data. Note: Age was only recorded to the nearest year for data from Centres B, C and D.</p

Characteristics of Gedling and replication COPD cases and controls.

<p>Characteristics of Gedling and replication COPD cases and controls.</p

Spirometry data from Delhi (Centre B) and Leicester (Centre G) according to GLI-Other reference.

<p>Spirometry data from Delhi (Centre B) and Leicester (Centre G) according to GLI-Other reference.</p

Association between extreme poverty and lung function in children residing in India.

<p>Association between extreme poverty and lung function in children residing in India.</p

Summary of studies included in the collation of South-Asian data.

<p>Summary of studies included in the collation of South-Asian data.</p

Spirometry data from South-Asian subjects according to GLI-South-East Asian reference.

<p>Spirometry data from South-Asian subjects according to GLI-South-East Asian reference.</p