Randomized Cross-Over Analysis of the Influence of Nitrogen Multiple Breath Washout on Spirometry in Monitoring Lung Function in Patients With Cystic Fibrosis and Primary Ciliary Dyskinesia.

Abstract

Background: When monitoring lung function in patients with Cystic Fibrosis (pwCF) and Primary Ciliary Dyskinesia (pwPCD), nitrogen multiple breath washout (N₂MBW) is usually performed before spirometry to prevent forced expiratory maneuvers from altering N₂MBW results. The N₂MBW may affect spirometry if cooperation decreases after a long period of examination or due to prolonged oxygen inhalation. The equivalence of these concepts has never been investigated in a randomized cross-over trial. We hypothesized that the order of pulmonary function tests (PFTs) would not influence the z-score FEV₁.

Methods: A total of 47 clinically stable outpatients (36 pwCF, 11 pwPCD; 16.7 ± 8.1 years) were randomized into two groups. Each patient underwent N₂MBW and spirometry at two consecutive visits (median interval 104 days): Group I: Spirometry followed by N₂MBW (A), reversed order at the second visit (B), Group II reversed (B→A).

Statistics: For the equivalence test, a change in z-score FEV1 (primary endpoint) ±0.2 and lung clearance index (LCI_2.5, secondary endpoint) ±15% was not considered relevant; therefore, changes outside this range were considered an intervention effect in the linear mixed model (p < 0.05).

Results: 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, LCI_2.5: -0.082; -0.3691 to 0.2054).

Discussion: In our cohort the order of PFTs has no influence on the results suggesting that a greater flexibility in practice is possible without the risk of falsifying results.

Trial registration: German Clinical Trials Register (No. DRKS00027473).