Multiple-breath washout (MBW) is a method to measure ventilation inhomogeneity (VI), defined by the lung clearance index (LCI). Breathing pattern and changes in functional residual capacity (FRC) impact the LCI, which can make results more difficult to interpret.

We aimed to design a VI index less sensitive to breathing pattern, changes in FRC and dead space, but with similar discriminative properties as the LCI.

We thus developed the "lung clearance ratio" (LCR). It normalizes the number of breaths required for a standard MBW test by the number of breaths predicted for a homogenously ventilated lung, based on the measured tidal volume, FRC, and dead space. The LCR was applied retrospectively to a data set of n=35 children (n=15 with cystic fibrosis (CF) and n=20 healthy controls (HC)), who performed MBW tests in both a relaxed tidal breathing (relaxed) and a fixed 1L breathing (fixed) protocols (Yammine S et al. J Cyst Fibros 2014;13(2):190-7).

Re-analysis of the dataset confirmed that LCI increased significantly in the fixed compared to relaxed protocol. Mean (SD, effect size, p-value) change in HC was +23.3% (24.8%, d=1.14, p<0.001) and in CF +25.3% (19.7%, d=1.11, p<0.001). Differences between protocols were substantially reduced when using the LCR, down to -2.0% (4.4%, d=0.49, p = 0.049) in HC, and +1.7% (10.3%, d=0.06, p=0.68) in CF. The LCR distinguished between HC and CF in both the relaxed (LCR_HC=1.17 (0.04), LCR_CF =1.72 (0.35), p<0.001) and the fixed protocols (LCR_HC=1.14 (0.05), LCR_CF =1.74 (0.35), p<0.001).

The LCR, a novel VI index for MBW measurements, appears to be more resistant to the impact of breathing pattern, while conserving the ability to distinguish HC and CF groups.