Background Longitudinal measurements of intra-breath respiratory impedance (Zrs) in preschool-aged children may be able to distinguish abnormal lung function trajectories in children with a history of wheezing compared to healthy ones.

Methods Children from a prospective, longitudinal community-based cohort performed annual intra-breath oscillometry (IB-OSC) measurements from age 3-years to 7-years. IB-OSC was performed using a single 10 Hz sinusoid while clinically asymptomatic. Linear mixed-effects models were developed to explore the effects of wheezing phenotypes, growth, and sex on seven IB-OSC outcome variables over time: resistance at end-expiration (ReE), resistance at end-inspiration (ReI), the tidal change in resistance (ΔR=ReE-ReI), reactance at end-expiration (XeE), reactance at end-inspiration (XeI), the tidal change in reactance (ΔX=XeE-XeI), and ΔX normalised by tidal volume (ΔX/VT).

Results Eighty-five children produced 375 acceptable IB-OSC measurements. Subjects were classified into one of three wheeze groups: never (n=36), transient (n=35), or persistent (n=14). After adjusting for height, children with persistent wheezing, compared to those who never wheezed, had -0.669 hPa·s·L -1 XeE (95% confidence interval [CI] -1.102 to -0.237, p<0.01), -0.465 hPa·s·L -1 ΔX (95%CI -0.772 to -0.159, p<0.01) and +1.433 hPa·s·L -1 ΔX/VT (95%CI +0.492 to +2.374, p<0.01). Increasing subject height had a significant effect on all IB-OSC resistance and reactance variables when adjusted for the effect of preschool wheezing.

Conclusions IB-OSC is feasible for tracking lung function in preschool-aged children, and intra-breath reactance outcomes may allow abnormal lung function to be identified early in asymptomatic children with a history of persistent wheeze.

PDS declares funding from the NHMRC (1102590, 1193840). PDS and ZH are named inventors of a patent owned by Telethon Kids Institute, Perth, Australia, covering lung function volume dependence. The techniques used in this study are broadly consistent with this patent licensed to Thorasys, Inc., Canada. PDS and ZH do not receive royalties from the Telethon Kids Institute or Thorasys. ZH declares consulting fees from Thorasys Thoracic Medical Systems Inc., Montreal, QC, Canada, and Piston Medical Ltd., Budapest, Hungary. KG declares funding unrelated to this study from the NHMRC and Medical Research Future Fund (MRFF) and is a member of the data safety and monitoring boards for four NHMRC and MRFF-supported clinical trials. MDW, RSW, SBL, SFZ, SS, and TB have no conflicts of interest to declare.

This study was supported by the National Health and Medical Research Council (GNT1078660). ZH was supported by Hungarian Scientific Research Fund (Grant K 128701). ZH and PDS were supported by the European Respiratory Society Clinical Research Collaboration Award (CRC_2013-02_INCIRCLE).

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Ethics committees of the Children's Health Queensland (HREC/13/QRCH/156) and The University of Queensland (2013001291) gave ethical approval for this work. This study was performed in accordance with the Declaration of Helsinki. All parents, guardians or next of kin provided written informed consent for all study subjects.

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