Feasibility and Variability of Measuring the Lung Clearance Index in a Multi‐Center Setting

Abstract

The Lung Clearance Index (LCI) is superior to spirometry in detecting early lung disease in cystic fibrosis (CF) and correlates with structural lung changes seen on CT scans. The LCI has the potential to become a novel outcome parameter for clinical and research purposes. However longitudinal studies are required to further prove its prognostic value. Multi-center design is likely to facilitate realization of such studies. Therefore the aim of the present study was to assess multi-center feasibility and inter-center variability of LCI measurements in healthy children and adolescents. Comparative measurements were performed in unselected patients with CF to confirm previous single-center results. LCI measurements were performed in eight centers using the EasyOne Pro, MBW Module (ndd Medical Technologies, Zurich, Switzerland). The overall success rate for LCI measurements was 75.5%, leaving 102/151 measurements in healthy volunteers and 139/183 measurements in patients with CF for final analysis. Age ranged between 4 and 24 years. Mean LCI (range of means among centers) was 6.3 (6.0-6.5) in healthy volunteers and thus normal. Inter-center variability of center means was 2.9%, ANOVA including Schffé procedure demonstrated no significant inter-center differences (P > 0.05). Mean LCI (range of means among centers) was 8.2 (7.4-8.9) in CF and thus abnormal. Our study demonstrates good multi-center feasibility and low inter-center variability of the LCI in healthy volunteers when measured with the EasyOne Pro MBW module. Our data confirm published LCI data in CF. However, central coordination, quality control, regular training, and supervision during the entire study appear essential for successfully performing multi-center trials.

Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report

“…Recent standardization work in device development and close collaboration between experienced operators suggest that previously reported between-center differences (15) may be avoidable with the use of commercial MBW equipment (16,17). Furthermore, efforts to standardize not only commercial equipment but also patient interfaces (face mask, tubing, etc.)…”

Is Lung Clearance Index (LCI) Affected by the Severity of Lung Disease in CF?

“…Spirometry is the most common widely used method for clinical monitoring of CF lung disease and the equipment is available in most respiratory centers. FEV 1 has proved to be a good predictor in subjects with moderate-to-severe CF lung disease [14,17,47,48], but it doesn't seem to be sensitive in earlier stages of the disease, as it is possible to have normal FEV 1 values when structural damages have already been developed on HRCT [20,[23][24][25]. Additionally, spirometry demands active cooperation to achieve technically acceptant curves, which may be difficult for infants and preschoolers [36,37].…”

“…The duration of a MBW test is on average 2-5 min per maneuver in a healthy subject, but longer in subjects with airway obstruction [47], while LCI success rate ranges between 70% to 85% in CF patients [48].…”

Decline in Lung Volume With Duchenne Muscular Dystrophy Is Associated With Ventilation Inhomogeneity

“…Normative data for LCI in healthy controls using the same equipment have been published previously. 17 At least 2 measurements with an inter-test variation of Ͻ 10% were recorded, and an example of online monitoring is shown in Figure 1.…”