Measures of Ventilation Inhomogeneity in Children With Cystic Fibrosis: Intra-breath Oscillometry Vs. MBW

Abstract

Rationale: Multiple breath washout (MBW) is the gold standard for detecting early changes in the peripheral airways suggestive of ventilation inhomogeneity in patients with cystic fibrosis (CF). Unfortunately, the feasibility of MBW is often low in very young children (30-40%) and can require significant time and staff availability to achieve results. Intra-breath oscillometry (IB-OSC) measures the respiratory system resistance (Rrs) and reactance (Xrs) during tidal breathing and has high feasibility (>80%) in very young children. Measures of Xrs by the IB-OSC technique include the small peripheral airways and are governed by the same physiological principles as MBW. Our aim was to explore whether measures of Xrs reflect ventilation inhomogeneity as measured by MBW. Methods: IB-OSC and MBW were performed on 91 children at the Queensland Children's Hospital, South Brisbane, Australia attending routine clinic visits as part of the Early Life Origins of CF (ELO) study. IB-OSC was measured with the TremoFLO device using a 10Hz signal to track within-breath changes, and MBW was performed using the N2 protocol. MBW results were classified as normal or abnormal (lung clearance index (LCI2.5%) >7.0) and measures of Xrs (end-expiratory (XeE), end-inspiratory (XeI), difference between end-expiratory/inspiratory (XeE-XeI) and the volume-dependence of reactance (ΔX/VT) were compared between the MBW groups using Mann-Whitney U test. Results: Acceptable paired IB-OSC and MBW measurements were achieved by 79 children (male 61%), median age 7.2yrs (IQR 5.1-10.3) and height 122.4cms (IQR 110.2- 143.3). Of those not included in the analysis, 66% were unable to achieve MBW results. Abnormal LCI2.5% results were reported in n=34 (43%). There were no differences in gender, age, height or CFTR mutations between those with normal vs. abnormal LCI2.5% results. Children with abnormal LCI results had significantly decreased (more negative) Xrs variable compared to children with normal LCI2.5% values (Table 1). Of those with abnormal LCI2.5%, 13 patients (38%) also had XeE-eI values below the lower limit of normal as previously defined by our team. Conclusion: These preliminary results suggest that IB-OSC Xrs variables may reflect ventilation inhomogeneity. More negative Xrs results were seen in patients with abnormal MBW results. The increased feasibility of IB-OSC over MBW in younger patients with CF may allow us to better detect and monitor early changes to lung function.