Early cystic fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index

The lung clearance index (LCI) is a sensitive non-invasive marker of early lung disease in young children with cystic fibrosis (CF), according to a new study from Australian researchers.

"We found that LCI is elevated early in children with CF, especially in the presence of airway inflammation and Pseudomonas aeruginosa," said Yvonne Belessis, MBBS, MPH, PhD, respiratory staff specialist at the Sydney Children's Hospital. "LCI may not only be a marker of early CF lung disease, but may be useful as an objective outcome measure in future studies of young children with CF."

The findings were published online ahead of print publication in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

LCI was determined after multiple breath washout (MBW) testing in 47 presymptomatic/minimally symptomatic infants and young children with CF (mean age 1.55 years) and 25 healthy control children (mean age 1.26 years). Bronchoalveolar lavage (BAL) was also performed in the children with CF.

Mean (SD) LCI in children with CF was 7.21 (0.81), compared with 6.45 (0.49) in control children (P<.001). The upper limit of normal for LCI was 7.41. Among the 47 children with CF, 15 (32%) had an elevated LCI. Measurements of LCI were repeatable and reproducible.

Airway infection (≥105 cfu/mL BAL fluid) was detected in 17 (36%) children with CF, including 7 (15%) children who had Pseudomonas aeruginosa infection. LCI in children with Pseudomonas was 7.92 (1.16), compared with 7.02 (0.56) in children without Pseudomonas (P=.038). LCI was significantly correlated with the BAL inflammatory markers interleukin-8 and neutrophil count.

There were some limitations to the study, including the lack of a robust measure of structural lung disease and a higher diagnostic threshold for airway infection than has been used in other BAL studies.

"We obtained reproducible measurements of LCI at the bedside of sedated infants and young children using a portable MBW system," said Dr. Belessis. "Compared with healthy controls, LCI was elevated in well infants and young children with CF, and abnormal LCI was associated with Pseudomonas aeruginosa infection and airway inflammation.

"Our results show that the LCI is a feasible, sensitive and repeatable non-invasive marker of early lung disease in well infants and young children with CF. Longitudinal assessment of the LCI taking into consideration changes in inflammation and airway infection over time are needed to confirm these findings."