The utility of moment ratios and abbreviated endpoints of the multiple breath washout test in preschool children with cystic fibrosis

Abstract

Background The multiple breath washout (MBW) test may be most useful in tracking disease progression over time to inform treatment decisions. In the clinical setting, alternative outcomes, which can be obtained quickly and easily, may facilitate interpretation of clinically relevant changes in lung function. Methods In this secondary analysis of data from 78 cystic fibrosis (CF) and 72 healthy control (HC) subjects between the ages of 2.6 and 5.9 years, MBW was performed at enrollment, 1, 3, 6, 9, and 12 months, as well as during symptomatic visits using the Exhalyzer D (EcoMedics AG, Duernten, Switzerland). The lung clearance index, LCI2.5, was compared to moment ratios (M1/M0 and M2/M0) at the standard cutoff (1/40th of starting tracer gas concentration) as well as LCI5 and moment ratios at 1/20th of the starting concentration (M1/M0 at LCI5, and M2/M0 at LCI5). Results All outcomes were able to distinguish between health and disease. LCI5 reduced testing time by 40% and increased feasibility by more than 10%. The limits of biological reproducibility in healthy children were similar between LCI2.5 (15%), LCI5 (12%), M1/M0 at LCI2.5 (14%), and M1/M0 at LCI5 (12%), but markedly larger for M2/M0 at LCI2.5 (30%) and M2/M0 at LCI5 (25%). Each outcome deteriorated significantly with worsening pulmonary symptoms, the magnitude of deterioration was greatest for M2/M0. Conclusions In preschool children with CF, LCI5 was more feasible to obtain and track disease progression. The second moment ratio was most sensitive to pulmonary symptoms, but had the greatest variability both within and between subjects.

Multiple breath washout: measuring early manifestations of lung pathology

“…There is strong evidence in support of using earlier cut-offs, namely LCI 5 at 1/20th of the starting concentration. The earlier cut-point can save considerable time (∼30–40%) and produces similar results in terms of repeatability, diagnostic characteristics, and detecting significant treatment effects [ 33 – 35 ]. Yet there is some concern that shortening the washout may reduce the sensitivity to detect lung function impairment [ 36 ].…”

“…The earlier cut-point can save considerable time (∼30-40%) and produces similar results in terms of repeatability, diagnostic characteristics, and detecting significant treatment effects [33][34][35].…”

Topic Sessions

“…Other parameters calculated from MBW include Moment Ratios (MR) and Slopes (S) of the 3 rd phase of certain breaths during the washout which allow differentiation of ventilation inhomogeneity in the convection dependent (Scond) and diffusion‐convection dependent (intra‐acinar) airways (Sacin). Because it requires tidal breathing only and no active co‐operation, it may be applicable at any age (2, 3); feasibility may increase in younger age‐groups by using a modified protocol and different parameters (4). An international consensus has been published; most recently, recommendations for using MBW in preschool children have been consented.…”

Cystic fibrosis year in review 2020: Section 2 pulmonary disease, infections, and inflammation

“…Also limiting the clinical utility of MBW is the length of the procedure itself and the required patient technique. One study tested whether alternate methods could increase MBW feasibility while still effectively monitoring disease progression and acute exacerbations 43 . Several varied measurements that allow for a shorter testing time were studied, including terminating at LCI with 1/20th the concentration of inert gas (LCI 5 ) compared to standard 1/40th the concentration (LCI 2.5 ).…”