Early detection of chronic obstructive pulmonary disease (COPD) using a novel technique for assessing lung unevenness (inhomogeneity)
| ISRCTN | ISRCTN46851791 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN46851791 |
| Secondary identifying numbers | DPG23\35 |
- Submission date
- 03/11/2023
- Registration date
- 17/01/2024
- Last edited
- 18/01/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Chronic obstructive pulmonary disease (COPD) affects 400 million people and is the 3rd leading cause of death worldwide. Patients suffer symptoms (cough/wheeze/breathlessness) that limit their quality of life. Approximately 70% of cases are caused by cigarette smoking. One reason for the poor outcomes is late diagnosis. The current tool used to diagnose COPD is a breathing test called spirometry. Results on spirometry only become abnormal when significant damage has already occurred and it cannot detect early or subtle changes in the small airways of the lung, which is where COPD starts.
Our research group at the University of Oxford has developed a new type of analyser that very accurately measures the flow of different gases breathed into and out of the lungs. We have also developed a mathematical approach to analysing these data that identifies unevenness (heterogeneity) in the lung and provides multiple new sensitive measures of lung function. In preliminary studies on small groups of people, we found that one of these measurements of heterogeneity show great promise as a sensitive marker of early problems in the small airways.
In this project, we want to understand more about the new measurements in people at increased risk for developing COPD, for example chronic smokers, and investigate whether our new test can be useful in detecting changes in lung function, earlier than is currently possible by the available breathing tests. To achieve this we will compare measurements of lung heterogeneity using our new test obtained in smokers (who have normal spirometry) and no diagnosis of airways disease with those obtained in non-smokers of the same age. Another aim is to compare our measures of lung heterogeneity with other lung function tests and to investigate their association with other disease markers (for example symptoms and airway inflammation).
Who can participate?
People between the ages of 25-60 years without a current diagnosis of respiratory disease can participate in the study. Both chronic smokers and non-smokers can participate.
What does the study involve?
The study involves a series of assessments of lung function, and a blood test. The lung heterogeneity measures are made using a 12-minute test during which the patient breathes normally through a mouthpiece, with their nose occluded by a nose clip. Each patient will breathe normal air for the first 7 min and then 100% oxygen for the final 5 min.
The other breathing tests that participants will be asked to perform are standard lung function tests such as forced spirometry, oscillometry and exhaled nitric oxide measurement. Participants will complete two questionnaires to allow us to assess their day-to-day lung health.
What are the possible benefits and risks of participating?
We do not expect participants in this research to benefit directly from their participation, but we hope that the results of the study will benefit patients in the future. We do not expect the gas mixtures breathed during this study to have any adverse health effects, and most patients studied with this technique so far have found the tests relatively easy to perform.
Where is the study run from?
University of Oxford and Oxford University Hospitals (UK)
When is the study starting and how long is it expected to run for?
May 2017 to December 2028
Who is funding the study?
This study is funded by ‘Asthma + Lung UK’, a charity working to improve lung health in the UK via research and campaigning.
Who is the main contact?
Nayia Petousi, nayia.petousi@ndm.ox.ac.uk
Contact information
Public, Scientific, Principal Investigator
Nuffield Department of Clinical Medicine
Division of Experimental Medicine
Oxford
OX3 7BN
United Kingdom
 ORCID ID |
0000-0002-5524-020X |
|---|---|
| Phone | +44 1865 857086 |
| nayia.petousi@ndm.ox.ac.uk |
Study information
| Study design | Observational cross-sectional cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | GP practice, Hospital, University/medical school/dental school |
| Study type | Diagnostic, Other, Screening |
| Participant information sheet | No participant information sheet available |
| Scientific title | A novel lung function Test foR Early dETection of chronic Obstructive Pulmonary disease (COPD) |
| Study acronym | TREETOP |
| Study hypothesis | We have developed a novel non-invasive method for measuring unevenness (heterogeneity) in gas-exchange across the lung. This provides multiple, new and sensitive physiological measures of lung function (heterogeneity indices). We hypothesise that these new lung heterogeneity measures will detect changes in lung function in chronic smokers, who are at risk of developing COPD, earlier than currently possible by the available diagnostic tools. |
| Ethics approval(s) |
Approved 17/05/2017, South Central Oxford A Research Ethics Committee (Bristol Research Ethics Committee Centre, Whitefriars, Level 3 Block B, Lewins Mead, Bristol, BS1 2NT, United Kingdom; +44 207 1048045; nrescommittee.southcentral-oxforda@nhs.net), ref: 17/SC/0172 |
| Condition | Chronic obstructive pulmonary disease |
| Intervention | This is an observational study in which indices of lung heterogeneity are measured in people who smoke but do not have diagnosed airways disease. A “Lung Heterogeneity test” is undertaken which involves breathing on a mouthpiece with the nose occluded for up to 15 minutes. During the test the inspired gas varies from breathing normal air (for 7-10 minutes) to breathing gas enriched with oxygen (up to 100% for a further 5 minutes). The composition of inspired and expired gas is analysed continuously using a novel in-airway gas analyser, and collected data are subsequently analysed using a mathematical model of gas exchange. Participants are also asked about their smoking, medical and drug history, as well as their symptoms using respiratory symptom questionnaires (COPD Assessment test, St George’s Respiratory Questionnaire). Participants also undertake additional clinical diagnostic tests of respiratory function, e.g. spirometry testing, measurement of exhaled nitric oxide (FeNO) and impulse oscillometry, and blood tests (e.g. FBC and CRP). All participants give written informed consent. |
| Intervention type | Other |
| Primary outcome measure | Lung heterogeneity indices: σlnCL (standard deviation of alveolar compliance distribution across lung volume), σVD (standard deviation of deadspace distribution across lung volume), VD (total anatomical deadspace), and VD/FRC (ratio of total deadspace to functional residual capacity) measured using the novel technique at the Research Visit in chronic current smokers (tobacco smokers of >= 10 pack-years) with non-obstructive spirometry vs non-smoker healthy controls |
| Secondary outcome measures | 1. Effect of participant pack years of smoking measured using smoking history data within questionnaires obtained at the Research Visit on the lung heterogeneity parameters. 2. Other potential markers of disease in smokers, e.g. markers of inflammation in blood (eosinophil count, CRP), exhaled nitric oxide and symptoms scores measured at the Research Visit and their correlation with the novel lung heterogeneity indices. 3. Other lung function measures: FEV1 % predicted , FEV1/FVC, FEF25-75%, measured with spirometry, and R5-R20, measured with impulse oscillometry at the Research Visit and their correlation with the novel heterogeneity indices. |
| Overall study start date | 17/05/2017 |
| Overall study end date | 31/12/2028 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 25 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 180 |
| Participant inclusion criteria | 1. Age 25-60 years 2. Current smokers with >10 pack years smoking history (Not applicable for the control group who are non-smokers) |
| Participant exclusion criteria | 1. Current diagnosis of respiratory disease 2. Pregnancy 3. Significant cardiovascular disease e.g. heart failure |
| Recruitment start date | 22/01/2024 |
| Recruitment end date | 31/12/2027 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Sherrington Building
Sherrington Road
Oxford
OX1 3PT
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Sponsor information
University/education
Clinical Trials & Research Governance
Joint Research Office
Boundary Brook House
Headington
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 1865 289885 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- Asthma UK, Asthma + Lung UK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/01/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | We intend to present the results of this study at academic conferences, and to submit reports of the study outcome for peer-reviewed publication in scientific journals. We also plan to participate in public and patient engagement events to present our projects and research. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available routinely, but requests for data sharing can be made to the study team. |
Editorial Notes
18/01/2024: The recruitment start date was changed from 01/01/2024 to 22/01/2024.
20/11/2023: Trial's existence confirmed by Asthma + Lung UK
