The lung clearance index (LCI) characterizes 2 distinct phenotypes in cystic fibrosis (CF) among pediatric patients with normal spirometry tests, indicating the likelihood of pulmonary exacerbation relapses, according to new findings published in BMC Pulmonary Medicine.

The LCI detects signs of early lung disease in individuals with CF using the Multiple-Breath Washout (MBW) test to measure ventilation inhomogeneity. Researchers questioned whether the LCI correlated with specific CF phenotypes, predicting the probability of pulmonary exacerbation relapses in pediatric patients with clinically stable spirometry values.

The investigators collected data on 125 children and adolescents under 18 years of age with CF who collectively underwent 313 MBW and spirometry tests between October 2014 and September 2019 at the CF Center of Milan, Italy. Participants required at least 2 MBW tests to analyze phenotypes over time.

The researchers collected disease-related data including pancreatic and nutritional status, the presence of CF-related diabetes, and Pseudomonas aeruginosa colonization which frequently contributes to pulmonary exacerbations. They recorded pulmonary exacerbation history and number of hospitalizations in the 12 months preceding the study.

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An algorithm separated the participants into 2 distinct clusters—cluster 1 characterized by pancreatic insufficiency and P aeruginosa colonization and cluster 2 without these negative prognostic factors. Spirometry tests detected forced expiratory values which indicated mild to normal airflow obstruction in 90.5% and 100% of patients in the 2 clusters, respectively. MBW tests detected ventilation inhomogeneity in 92.3% of cluster 1 patients compared with 42.6% of cluster 2 patients.

After 4 years, 91.2% of children (n=114) in the study experienced at least 1 pulmonary exacerbation, ranging between 0 and 4. Disease severity increased as the number of events increased. After study initiation, children in cluster 1 lasted a median of 0.30 years (range: 0.15-0.71) before their first pulmonary exacerbation, while children in cluster 2 lasted a median of 1.19 years (range: 0.46-2.89).

“Our findings describe for the first time an association between phenotypes based on ventilation inhomogeneity and the risk of [pulmonary exacerbation] relapse in children and adolescents with CF,” the authors said.

“These results remind us of the paramount importance to delay the occurrence of [pulmonary exacerbation] and to concentrate the efforts of the multidisciplinary team to preserve lung function, especially in terms of ventilation homogeneity in children.”


Gambazza S, Ambrogi F, Carta F, et al. Lung clearance index to characterize clinical phenotypes of children and adolescents with cystic fibrosis. BMC Pulm Med. 2022;22(1):122. doi:10.1186/s12890-022-01903-5