Electra

Who is eligible for the study? 

Inclusion Criteria

• Patients (aged 16 years and over) who have undergone double lung or heart-lung transplantation at Manchester Cardiothoracic Unit within the last 6 months-5 years.

• Clinically stable at screening

Exclusion criteria

• FEV1 ≤65% best post-operative value at screening
• Current ongoing infection with epidemic strains of B. cepacia, M abcessus or other organisms with specific infection control implications
• Patients with evidence of active acute bacterial, viral or fungal infection not successfully resolved at least 4 weeks prior to the screening visit. Patients with chronic or ongoing non-transmissible infections, such as pseudomonas aeruginosa, are eligible for the study.
• Patients with acute cellular rejection and antibody-mediated rejection at screening
• Patient has baseline resting oxygen of < 92% on room air, or use of supplemental oxygen
• Other significant co-morbidities that are likely to interfere with study assessments, as judged by the research team

Multiple Breath Washout (MBW)

MBW is performed during simple relaxed breathing. Participants will be seated, with a nose clip applied to ensure no air leaks via the nose. The first part of the test involves breathing air mixed with a small amount of a tracer gas, called SF6 (sulphur hexafluoride), through a mouthpiece. This gas is present in very small amounts, is inert, odourless and colourless and is not taken up by the body. It has been used for many decades in assessing lung function in similar tests, including in infants and young children. During the test, participants will breathe the air and tracer gas in and out for a few minutes until it is evenly mixed with the air in your lungs (this phase of the test is known as the washin). At this point participants will be switched to breathing room air, and we will measure how the tracer gas is breathed out of the lungs. This second phase is known as the washout.

The entire test (washin and washout) should not take more than 10 minutes, and we will repeat this three times. The washin process will involve breathing the mixture of air and tracer gas, with additional oxygen, from a sealed bag. The washin performed in this way should only take 2-3 minutes. The gas mix has additional oxygen, and waste gas (carbon dioxide) will be removed to ensure that breathing remains comfortable.

Considerable evidence over the last decade has demonstrated that LCI is very much more sensitive than spirometry at detecting and monitoring a variety of airway diseases, particularly cystic fibrosis (CF), and that the test is feasible and practical even in very young children.

LCI is a measurement that has been shown to be especially sensitive to early airways disease when spirometry is still within the normal range. It has been shown in CF to correlate with important clinical markers of disease severity and to predict future lung function decline. LCI has now been adopted into clinical monitoring in CF in some specialist centres and has been used in several clinical trials of new CF therapies. 

Forced Oscillation Technique (FOT)

The second test we are doing is called the Forced Oscillation technique (FOT), a quick non-invasive test which uses sound waves to measure blockages (or resistance) in the small airways.

This is an alternative effort-independent method of assessing the peripheral airways. Participants will be seated and asked to breathe normally through a mouthpiece whilst holding your cheeks. The device delivers low pressure soundwaves to the lungs and the resulting vibratoins in gas pressure within the airways allow calculation of resistance to airflow. The test will be performed three times and the whole test should take no more than 3-5 minutes. 

Spirometry

As per usual standard of care for post-transplant follow-up, participants will also undergo spirometry as normal at every visit.

Hyperpolarised MRI

Hyperpolarised gas MRI (HP-MRI) is a specialised lung imaging technique that has the additional advantage of direct 3-dimensional visualisation of lung ventilation. As part of the ELECTRA study, participants will be asked to undergo one MRI scan per year for the duration of the study. During the scan, participants will inhale an inert tracer gas (Xenon), followed by a single breath hold. This test is radiation free and will provide images of how well gas is mixing in different regions of the lungs.

Before going into the scanner a trained physiologist will describe the test and practice the breathing procedures with you. The MRI scans will take approximately 1hour, but breaks to walk around or take a drink can be provided if they are needed. 

During the hour we take different images of the lungs. Some of these images involve breathing in a gas from a bag. This will be delivered by a physiologist whilst you are lying in the scanner. After taking a breath of the gas (a mixture of nitrogen and xenon), participants will be asked to hold their breath for up to 15 seconds, during which the images are taken.

If participants are happy to have a cannula (thin tube) put into a vein, during one of the scans we will inject gadolinium contrast into the cannula to look at the flow of blood through the lung. A dedicated radiographer or physicist with experience in doing this will talk participants through the whole process before and during the scans.

Bronchoscopy

Patients routinely undergo surveillance bronchoscopy as part of post-transplant follow-up, which occurs at certain time points dictated by the clinicians. The procedure is carried out under intravenous sedation and local anaesthesia in a dedicated procedure suite. Participants will not be asked to undergo any additional bronchoscopies purely for research purposes as part of this study. We will however collect additional airway samples for further analysis when these procedures take place. These samples will undergo specialist testing for inflammation and infection.
 

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