The order does not matter! – A randomized cross-over analysis of the mutual influence of Multiple Breath Washout and Spirometry in children with Cystic Fibrosis and Primary Ciliary Dyskinesia

<bold>Background:</bold> To monitor lung function in patients with Cystic Fibrosis (pwCF) and Primary Ciliary Dyskinesia (pwPCD), Multiple Breath Washout (MBW) is performed first, followed by Spirometry to prevent forced expiratory manoeuvres from altering the MBW and confounding the results. The MBW may affect spirometry if cooperation decreases after prolonged testing or if pure oxygen is inhaled. The equivalence of these concepts has never been investigated in a randomized cross-over trial. We hypothesized that the order of pulmonary function tests would not affect FEV1 z-score. <bold>Methods:</bold> 47 clinically stable outpatients (36 pwCF, 11 pwPCD; 16.7 ± 8.1 years) were randomized into two groups. Each patient underwent MBW and Spirometry at two consecutive visits (median interval 104 days): Group I started with Spirometry followed by MBW (A), with the order reversed at the second visit (B), Group II reversed (BàA). Statistics: For the equivalence test, a change in z-score FEV1 ±0.2 and lung clearance index (LCI2.5%) ±15% was not considered relevant; therefore, changes outside this range were considered an intervention effect in the linear mixed model (p<0.05). <bold>Results:</bold> There was a significant deterioration in z-score FEV1 between the two appointments (period effect: -0.177; p=0.012). The intervention effect and 95% confidence interval were within the equivalence range in both groups (z-score FEV1: 0.039; -0.0765 to 0.1539, LCI2.5%: 0.058; -0.082 to 0.578). <bold>Discussion:</bold> The order of pulmonary function tests has no influence on z-score FEV1 or LCI2.5%, allowing greater flexibility in clinical practice.