One-year evolution and variability in multiple-breath washout indices in children and young adults with primary...

Background and objective: Cross-sectional and longer-term studies have demonstrated abnormal yet stable multiple-breath inert gas washout (MBW) indices in patients with primary ciliary dyskinesia (PCD). This study aimed to assess the intermediate term evolution and the between-occasion variability of MBW indices in PCD over 1 year. Methods: Children and young adults with a confirmed diagnosis of PCD were included in this single-centre, prospective, observational, longitudinal study. Over 1 year, nitrogen (N₂) MBW and spirometry were performed at three occasions during ordinary scheduled outpatient visits. Trends and variability in lung clearance index (LCI), moment ratios, normalized N₂ concentration at six lung volume turnovers, and regional ventilation inhomogeneity indices of the conducting and intra-acinar airways (S_cond*V_T and S_acin*V_T) were analysed using linear mixed models. Results: Forty-two patients, aged 6-29 years (median: 15.4), performed 116 N₂ MBW test occasions and 96.6% were technically acceptable. A minimal, although significant, increase in LCI over 1 year (mean: 0.51 units, 95% CI: 0.12-0.91, p = 0.01) was found; while, all other N₂ MBW indices and FEV₁ remained unchanged. A moderate correlation was observed between LCI and FEV₁ (r = -0.47, p = 0.0001). The limits of agreement between tests 1 year apart were for LCI: -1.96 to 2.98; S_cond*V_T: ± 0.039; S_acin*V_T: -0.108 to 0.128. Conclusions: Children and young adults with PCD managed at a specialist centre showed slightly, but significant, increasing LCI and otherwise unchanged ventilation inhomogeneity indices and dynamic volumes over the intermediate term of 1 year. Estimates of the variability of N₂ MBW indices may inform sample size calculations of future randomized controlled trials.