Evolution of lung clearance index during the first year of life in cystic fibrosis

Abstract

Background: Early lung development is crucial for long-term lung function and respiratory morbidity. During this vulnerable period, respiratory events (e.g. inflammation and infection) can result in lifelong deficits, especially in patients with cystic fibrosis (CF).

Aims: To compare multiple breath washout (MBW) outcomes in healthy infants (HC) and infants with CF and assess the longitudinal development over the first year of life.

Methods: We included data from the prospective Basel-Bern infant lung development and Swiss CF infant lung development cohorts. MBW was performed with sulfur hexafluoride using an ultrasonic flowmeter (Exhalyzer D, Ecomedics AG). Data were analyzed (WBreath 3.52.3, ndd AG) in accordance with current consensus guidelines.

Results: Acceptable MBW data was available in 432 infants (70 CF). Baseline mean (SD) functional residual capacity (FRC) for healthy infants at 6 weeks was 22.2 (3.3) mL/kg and lung clearance index (LCI) was 7.3 (0.8) TO. The upper limit of normal (ULN; mean+1.64SD) was 27.5 mL/kg for FRC and 8.7 TO for LCI. Infants with CF had higher FRC (+3.0 mL/kg, p<0.001) and LCI (+0.2 TO, p=0.09) compared to healthy controls at 6 weeks of age. In CF infants, LCI significantly deteriorated by 1 year of age to 9.7 (1.8) TO (n=43; p<0.001). LCI at 1 year was associated with LCI at 6 weeks (r_s=0.30, p<0.01).

Conclusion: Lung function was comparable between healthy controls and infants with CF at 6 weeks but deteriorated over the first year of life in infants with CF. Next steps will be to identify the determinants of increased ventilation inhomogeneity at 1 year. These data will enable targeted prevention strategies for patients at risk and help to preserve lung function.