DiagnosticInnovation Novel innovative ways to screen lung function in cystic fibrosis patients
For decades, lung health in the life-limiting disease, cystic fibrosis, has been measured by spirometry, a lung function test based on a forced blow. Whilst this has served well for groups with established lung damage (bronchiectasis), it measures mainly the central airways, lacking sensitivity in children. Since the widespread availability of highly effective modulator drugs detecting improvement, stability or disease progression is also a challenge for many adult patients.
The lung clearance index (LCI) is much more sensitive to early/ moderate disease. On behalf of the European CF Society, we established the LCI Core Facility at the Royal Brompton/ National Heart and Lung Institute. Over the last decade, we have standardised the methodology and trained >150 international operators. This standardisation has led to its acceptance by regulatory agencies as the primary outcome for multiple drug trials in children, leading to license extensions into younger ages. For a progressive disease, early initiation of effective therapy is essential, providing potential life-long benefits and being part of global Standards of Care. We have recently developed a further improvement to this test, adding in a short extension to detect silent areas of lung damage (LCIShX). This is being adopted internationally and the software added to the device by the manufacturers.
One disadvantage of physiology-based tests is their lack of localisation: multiple small areas of damage may yield the same result as one more substantial area, but treatments required may differ. CT scans are used sparingly in CF as they have an associated radiation burden. The CF research team at NHLI & Brompton have collaborated with Bioxydyn on a programme using functional (oxygen-enhanced) MRI, with no associated radiation. Used together, LCIShX and OE-MRI were able to detect declining lung health in people receiving CFTR modulator drugs who appeared stable with conventional measures.
Through national (Respiratory Translational Research Collaboration) and international (European Cystic Fibrosis Society, European Respiratory Society) networks, we are increasing awareness of these optimised outcome measures, and training colleagues in the techniques. Wider adoption of these tools will allow personalised therapy decisions, which will reduce burden of treatment whilst limiting ‘invisible’ deterioration, improve lung health of younger people living with CF and build a cadre of physiology/ imaging investigators with a focus on CF and associated lung conditions.
