Elastin degradation in exacerbations of AATD (V.1)
Research type
Research Study
Full title
Elastin degradation in exacerbations of Alpha 1 antitrypsin deficiency (AATD) lung disease
IRAS ID
211141
Contact name
Alice Turner
Contact email
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Summary of Research
This project is designed to investigate break down of an elastic protein (elastin) within the lungs of patients with alpha 1 antitrypsin deficiency (AATD) who have chronic obstructive pulmonary disease (COPD), and to determine whether chemicals in the urine may enable measuring this at home.
Patients with AATD are susceptible to COPD exacerbations as they lack alpha 1 antitrypsin, a substance which reduces the activity of another chemical called neutrophil elastase (NE). NE acts to break down elastin within the lungs. During exacerbations, inflammation in the lungs leads to increased activity of NE.
One issue with treating COPD exacerbations at present is that patients often do not recognise exacerbations and receive prompt or indeed any treatment. A test patients could perform at home which measured elastin breakdown may enable rapid recognition of exacerbation. Desmosine is a chemical which is an indicator of elastin breakdown, and is found in urine. Home urine monitoring could provide a simple, non-invasive measurement to facilitate quicker recognition.
Participants will include patients with AATD and healthy controls. All will give informed consent. The trial is observational, meaning no aspect of regular treatment will be changed. Participants will be followed up for 18 months. Initially they will undergo clinical review, consisting of non-invasive lung function tests, questionnaires, blood, urine and sputum sampling. They will be asked to keep a symptom diary for the duration of the study. When well, patients will be asked to test urine weekly at home. If exacerbation is suspected, they will be asked to test their urine and attend again for clinical review. Standard treatment will be initiated, and the patient will be asked to monitor urine at home before attending another visit for clinical review on day 56 post exacerbation.
Summary of Results
A total of 130 participants were recruited (55 with AATD and 75 healthy controls) to the study. During the stable state patients with AATD were required to perform weekly home urine measurements (using a POC urine cube device), with this increasing to daily monitoring for 7 days from Day 1 of initiation of treatment for an exacerbation. Of the AATD patients enrolled 45 completed the required study visits. Patients were also issued with an electronic symptom diary (e-Diary) for BronkoTest® and they were required to complete this every day for the duration of the study.
Results of this study demonstrated that subjects found the eDiary and POC urine cube device easy to use, thus making them feasible methods for home monitoring of exacerbations in patients with AATD. However, the use of urinary biomarkers across numerous pathways showed no clear distinction between stable, exacerbation or recovery states though it is likely related to the timing of when samples were taken rather than the underlying pathophysiology.
Exacerbations were typically found to last longer with the higher symptom burden seen in Type I exacerbations. Treated exacerbations also tended to be longer with a higher symptom peak in comparison to untreated exacerbations.REC name
Wales REC 6
REC reference
16/WA/0352
Date of REC Opinion
2 Nov 2016
REC opinion
Favourable Opinion