Abstract
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 (N(2)) MBW and spirometry were performed at three occasions during ordinary scheduled outpatient visits. Trends and variability in lung clearance index (LCI), moment ratios, normalized N(2) 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 N(2) 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 N(2) MBW indices and FEV(1) remained unchanged. A moderate correlation was observed between LCI and FEV(1) (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 N(2) MBW indices may inform sample size calculations of future randomized controlled trials.