As part of RECOVER, patients with CF will undergo several tests at baseline and then at regular intervals. These tests include:
Lung Clearance Index:
LCI is a simple breathing test involving normal quiet breathing through a mouthpiece. It involves breathing in 100% oxygen for a few breaths and then measuring the gases that are breathed out to determine if there is any slowing down of airflow in the lungs. The test takes about 20-30 minutes overall as the procedure is repeated three times for accuracy. LCI will be performed at baseline and then 6 monthly for 2 years.
Ultra-low dose, spirometry-controlled CT scanning:
A CT scan is a detailed three-dimensional image of the inside of the lungs and airways. It allows us to collect detailed information in relation to CF lung disease. CT scans extremely helpful in CF but are associated with radiation, so they must be used carefully over a person’s lifetime. The type of CT needed in CF can be performed with substantially less radiation than a standard CT scan. Many centres around the world perform low dose CT scans every two years in people with CF as part of annual assessment. Our partners in the LungAnalysis Core in Erasmus, Rotterdam have been working with hospitals around the world to standardise CT scanners, advise on ultra-low dose protocols and analyse the results. LungAnalysis has worked with each centre in RECOVER to standardise scanners and help keep doses down. Scans will be needed for RECOVER at baseline, year one and year two. Scans that are used as part of standard care can be used for RECOVER as long as the protocol is the same (we are standardising this in all sites).
Sweat chloride is a painless procedure and will be performed on both arms. Two small electrodes are placed on the arm with a gel disc for 5 minutes to stimulate sweating. Then a small sweat collecting “watch” is placed on the arm to collect the sweat. This takes roughly around 45 minutes in total to complete (30-minute sweat collection time per arm). This will be performed at baseline, the initiation of TCMT (these may be the same in many subjects), 3 months, 1 year and 2 years. Sweat will be analysed on samples using a specialised machine at each centre. This information will then be input into the database by the CF researcher.
Nasal lavages will only be performed on participants 12 years and over. These will be performed at baseline, 6 months and 1 year. A nasal lavage is a technique in which the nasal cavity is washed to flush out mucus from the nose and sinuses. 10mls of sterile saline will be slowly washed into each nostril with the participants head reclined. This stays in the airways for 10 seconds before the participant leans forward and allows the saline to drain into a collection container. This is a painless assessment that takes about 5 minutes to perform. The participant will be coached on the technique prior to sample collection by the CF research coordinator/nurse. This will allow us to track nasal inflammation through RECOVER by measuring inflammatory mediators and any bacterial that may be present within the lavage.
Exhaled Nitric Oxide (FeNO):
Nitric oxide (NO) is an important molecule produced by airway cells that is related to inflammation and defense against bacteria. FeNO has been shown to be abnormally low in people with cystic fibrosis. The CFTR modulator Ivacaftor has been shown to lead to a significant increase in levels of FeNO in PWCF. We are therefore interested to see the impact TCMT may have on FeNO measurement. FENO will be measure with the Niox VERO device via a mouthpiece during normal relaxed breathing. The study coordinator will train subjects on how to perform this. This assessment will take less than 5 minutes.
As per routine clinical practice, most people with cystic fibrosis from 6 years of age onwards have annual liver ultrasound scans as part of annual assessment. An ultrasound is a painless procedure that takes less than 10 minutes to perform. The ultrasound scan will be performed at baseline and at one and two years after commencement on Triple Combination CFTR modulator therapy (TCMT). We will link in with the radiology department in each hospital to collect the relevant information when routine scans are being performed, so repeat tests for RECOVER are not necessary. For centres where annual ultrasound is not performed every year, we will ask that a scan is performed each year for RECOVER.
As part of standard clinical care, sputum or throat swabs will be collected and processed in clinical laboratories. We will collect the information on the results and upload it onto our database. Separate to this, sputum samples for research purposes will be collected either spontaneously or after hypertonic saline induction (where possible) at study visits for measurement of markers of inflammation. Sputum for inflammation will be required at baseline, 6 months, one year and two years.
Stool sample collection:
Inflammation in the gut can easily be measured in stool samples. A stool sample will be collected from study participants at baseline, commencement on TCMT, 1 month after, 6 months after and after 2 years. A sample collection equipment will be provided in advance to subjects and parents, so that samples can be collected on the morning of a study visit.
Abdominal Symptom Score:
Our collaborators in Brandenburg, Germany have developed a specific abdominal symptom questionnaire for people with CF. The CFAbd score is validated in children and adults with CF and scores correlate well with ultrasound findings and gut inflammation. The CFAbd score has been used in studies in leading international centres. This questionnaire will take 5-8 minutes for the first time and 3-5 minutes on subsequent occasions. Questionnaires will be delivered at centres by the local research coordinator. The questionnaire will be collected at baseline, 6 months and 2 years in all subjects, and in people commencing on TCMT, 1 month after and 2 months after treatment.
Cystic Fibrosis Questionnaire – Revised (CFQ-R):
Over the last few decades a growing recognition of the importance of patient reported health related quality of life indices has developed. These indices are now recognized by patient organisations, clinicians and regulators as a vital tool in the development and testing of new treatments in people with cystic fibrosis. The Cystic Fibrosis Questionnaire-Revised (CFQR) is a specifically designed quality of life questionnaire for people with CF. We will utilise CFQ-R, the CFQ-R treatment burden questionnaire and the CFQ-R sinus symptom scale in this study. The CFQ-R sinus symptom questionnaire will be delivered to individuals undergoing nasal lavage at each time point. The CFQ-R treatment burden questionnaire is used to assess treatment burden in people with CF and assess to what extent do treatments make daily life difficult; how much time is spent on treatments and how difficult it is to do treatments every day? CFQ-R, including the treatment burden subscale, will be delivered at baseline, 6 months, one year and two years.
Pharmacy and MEMs Caps:
As part of assessing adherence to treatments, prescribed medications at an individual level will be tracked throughout the study. A number of methods will be used to monitor and understand treatment adherence including electronic medication event tracking systems (MEMs), self-reported adherence and medication possession ratio (MPR) based on pharmacy pick up rates. MEMs is the gold standard for electronic monitoring. It mimics a traditional pill bottle with the enhanced ability to track the date and time of each bottle opening. Adherence to TCMT will be measured with MEMs in a subset of participants in Dublin centres only. Self-reporting adherence will be collected using an up to date version of a specifically designed adherence scale for children and adults with CF. The study also includes collection of pharmacy records from each subject’s community pharmacy with the consent of the subject/parents. This data will not be shared with the local CF Team (just the RECOVER researchers).
Other clinical parameters in medical notes:
Other routine health measurements will be collected from subject’s medical charts with consent. Data collected will include the following:
• Lung function measurements
• Liver blood tests
• Nutritional measures such as height, weight and BMI
• Airway sample microbiology results
For more information about RECOVER and the assessments involved please contact us at info@RECOVERCF.ie.