New sensitive lung tests reveal hidden progression in people with CF
Researchers say 2 new tools spotted changes missed by current methods
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Using two new sensitive lung tests, researchers in Europe were able to identify subtle changes indicating worsening cystic fibrosis (CF) in people with the genetic disease — even when standard breathing assessments showed stable lung function.
These tests — an oxygen-enhanced MRI and the multiple breath washout with Short extension, or MBWShX — may work better than current tools for detecting ongoing lung disease progression in CF patients, according to a new study detailing their use. The results, the researchers say, highlight the need for more sensitive monitoring tests for assessing CF lung disease.
“Our findings suggest that oxygen-enhanced MRI and MBWShX may provide additional information beyond conventional tests and could help us better understand what is happening in the lungs over time,” Christopher Short, PhD, the study’s lead author at the Imperial College of London’s National Heart and Lung Institute in the U.K., said in a university news story.
The researchers say they’re now planning larger multicenter studies to validate these tests.
The study, “Oxygen-enhanced MRI and multiple breath washout with Short extension reveal cystic fibrosis lung disease progression despite triple modulator therapy,” was published in the journal Thorax.
The thick mucus that characterizes CF builds up in the lungs, blocks the airways, and leads to ongoing infections — all of which contribute to permanent damage and a decline in lung function.
Lung function now mainly assessed with spirometry test
Lung function in CF is typically assessed using spirometry, a measure of the amount of air that can be rapidly exhaled.
An alternative test with greater sensitivity is the multiple breath washout (MBW), which generates what’s known as the lung clearance index, or LCI. It’s a measure of the number of times the air remaining in the lungs at the end of a normal, relaxed exhalation has to essentially be turned over to clear a tracer gas; a greater number indicates worse lung function.
Lung testing has become even more crucial in recent years, the researchers noted, given the development of a new class of medications, called CFTR modulators, that have markedly improved lung function and quality of life for many people with CF.
However, according to the team, as CF becomes milder and progresses more slowly with these meds, traditional monitoring tools such as spirometry and MBW may not catch low levels of ongoing lung function decline in CF patients.
“CFTR modulators have had a transformative impact on the lives of people with cystic fibrosis,” said Short. “As patients become healthier, it becomes increasingly important that our monitoring tools are sensitive enough to detect subtle changes in lung disease.”
Researchers have now addressed these limitations by adding a slow, forced exhale at the end of the MBW test, called the Short extension, or MBWShX. This generates two new measures: an overall score known as the LCIShX and UVLU, or under-ventilated lung unit, which estimates the amount of poorly ventilated lung, previously referred to as trapped air.
Still, using this test can’t provide information about the location of lung damage. To complement the MBWShX tests, the team applied oxygen-enhanced MRI (OE-MRI), an imaging technique that uses inhaled medical oxygen to highlight how well different areas of the lung are ventilated. It can be performed on standard MRI scanners, without radiation exposure.
New MRI, breathing tests shown to be more sensitive
To assess the new tests alongside standard measures, Short and other researchers in the U.K., Ireland, and the Netherlands followed 46 people with CF, ages 6 to 55, over 18 months. A subgroup of 20 people with CF and 20 age-matched healthy volunteers also underwent repeated testing within six weeks.
Nearly all participants tolerated the MRI and breathing tests well; two were unable to complete an MRI due to claustrophobia. The results were stable when repeated within six weeks in both healthy volunteers and people with CF, meaning the tests were precise enough to track real change over time rather than random variation.
The tests also clearly distinguished CF patients from healthy controls and were more likely to detect abnormality than standard tests. At the study’s start, 41% of people with CF had an abnormal FEV1, a spirometry measure. Half of the patients had an abnormal LCI, while 80% had an abnormal LCIShX and 85% had abnormal UVLU results.
These findings challenge reliance on [standard lung function tests] alone to assess disease stability in the modulator [treatment] era.
Among a smaller group of 11 school-age children who had recently started treatment with Trikafta, a CFTR modulator, FEV1 and LCI did not show significant improvement over the first six months. Instead, LCIShX improved by 2.5 units and UVLU by 1.8 units, while on OE-MRI, the ventilation defect percentage (VDP), a measure of poorly ventilated lung, dropped by 1.6%, and the ventilation signal improved.
Among those already on Trikafta therapy for at least six months and followed for up to 18 months, spirometry measures, such as FEV1 and forced vital capacity, as well as LCI and MRI structural scores, did not change significantly, suggesting stable disease by standard methods, the researchers reported.
By comparison, LCIShX worsened by 1.53 units over 18 months, with slightly more than half (54%) of participants showing a change of more than 10%. UVLU also worsened by 1.1 units by 18 months. On OE-MRI, VDP rose by 2.5% at 12 months and 4.5% at 18 months, while the ventilation signal weakened significantly at both time points.
The team noted that those with worse lung function at baseline, or the study’s start — as assessed by spirometry, LCI, or LCIShX — had greater lung function decline during the study period than those who did not. Similar lung function changes were also found among those with chronic Pseudomonas aeruginosa infection and pulmonary exacerbations, or a sudden worsening of symptoms, at baseline.
Overall, the researchers concluded that “MBWShX and OE-MRI are sensitive, reliable methods for the monitoring of CF lung disease.”
The team also noted that “these are the first data suggesting that lung disease is still progressing in [CF patients] over time despite [Trikafta] therapy.”
Given the results, “these findings challenge reliance on [standard lung function tests] alone to assess disease stability in the modulator [treatment] era,” the scientists wrote.
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