Lung Clearance Index Test May Best Identify Children at Risk of Flares
A noninvasive measure of lung function called lung clearance index (LCI) could be used to identify children and adolescents with cystic fibrosis (CF) who are at higher risk of a pulmonary exacerbation, an Italian study found.
Notably, this work involved patients with normal or mildly reduced forced expiratory volume in one second (FEV1), a common measure of lung health based on how much air a person can quickly exhale. As such, LCI may be more useful to differentiate among patients than FEV1.
The study, “Lung clearance index to characterize clinical phenotypes of children and adolescents with cystic fibrosis,” was published in the journal BMC Pulmonary Medicine.
Lung clearance index “is the main derivative of the multiple breath washout test (MBW), and it has gained lot of attention during the last years as a promising outcome measure in cystic fibrosis (CF), complementary to conventional spirometry,” the researchers wrote.
Of note, FEV1 is a key spirometry measurement.
LCI is assessed by having a person inhale a “tracer gas,” and then seeing how long it takes for that person to “clear” the tracer gas from their lungs. Higher LCI values are typically associated with structural changes in the lungs, indicating worse lung function.
This measure is accepted as an early marker of CF lung disease, especially in children with normal spirometry — suggesting normal lung function.
However, whether LCI can be used to identify subgroups of pediatric CF patients with more severe lung disease, who may benefit from more intensive or targeted therapies, remains unclear.
A research team led by those at the CF Center of Milan characterized children and adolescents with CF into different clusters or groups based on data generated in a first MBW assessment, which included LCI.
They also evaluated whether these LCI-based clusters represented patients with different risks of pulmonary exacerbation, or episodes of a sudden worsening in respiratory symptoms, within four years. When these episodes occur too often or go untreated, patients could be at risk of permanent lung damage.
Their study involved 125 children and adolescents with stable CF at the time of a first MBW assessment at the CF center, and who had completed at least one other MBW assessment in those four years — between October 2014 and September 2019.
These patients (64 boys and 61 girls) had a mean age of 11.4 (range, 5.5–16.8 years) and completed 313 MBW tests during the study period. Most (91.2%) had at least one exacerbation, or flare, during the four years of follow-up. The mean number of flares was 2.3.
Results showed two distinct clusters of patients, all of about the same age and nutritional status, and fairly divided by sex, but who differed in several clinical features. Cluster 1 include children and adolescents with more severe CF.
Relative to cluster 2, cluster 1 patients were the only group to have pancreatic insufficiency and were more often infected with Pseudomonas aeruginosa (85.4% vs. 52.6%) — two known predictors of more severe disease.
These children had significantly higher LCI values — which were also more often above the normal upper limit (92.3% vs. 42.6%) — and significantly lower FEV1. However, 90.5% of the children in cluster 1 and all of those in cluster 2 had FEV1 values within normal range or only mildly lower than normal.
“Although statistically different between the two clusters, FEV1 remains above 90% predicted,” the researchers wrote. “This reinforces its poor sensitivity in discriminating lung health in patients with CF during childhood and adolescence, as already reported” in previous studies.
In the year prior to a first MBW test, cluster 1 patients also had a significantly higher median number of exacerbations (three vs. none), and only children and adolescents in cluster 1 had been hospitalized that year.
These data suggest that pediatric CF patients in cluster 1, characterized by significantly higher LCI values, are at increased risk of worse lung disease and may need personalized, intensive interventions.
In agreement, cluster 2 patients took longer than those in cluster 1 to experience a first pulmonary exacerbation (1.19 vs. 0.3 years), reflecting a 55% lower risk of a flare relapse.
Findings highlight that “LCI is useful in clinical practice to characterize distinct [clusters] of children and adolescents with mild/normal FEV1,” and that “a less severe [cluster] translates into a lower risk of PE [pulmonary exacerbation] relapse,” the researchers wrote.
Study findings also “add to the available literature in confirming the clinical utility of [MBW] to monitor lung disease during childhood and adolescence in CF,” they added.