Figures
- FIGURE 1
Bland–Altman plots for lung clearance index (LCI)1/40th and LCI1/20th within and between visits. Bland–Altman plots for LCI1/40th within visit repeatability, LCI1/20th within visit repeatability, LCI1/40th between visit (8 week) repeatability and LCI1/20th between visit (8 week) repeatability. LoA: limits of agreement 95% confidence interval.
- FIGURE 2
Correlations between lung clearance index (LCI)1/20th and LCI1/40th washout test. Correlations between lung clearance index and 1/40th and 1/20th washout concentrations. Plotted with a line of best fit and the confidence intervals (dotted line).
- FIGURE 3
Correlations between forced expiratory volume in 1 s (FEV1) % predicted and a) lung clearance index (LCI)1/20th, b) LCI1/40th, c) Scond conducting zone and d) Sacin acinar zone. Correlations between measures of multiple-breath washout and forced expiratory volume in 1 s per cent predicted (FEV1 %). GOLD: Global Initiative for Chronic Obstructive Lung Disease.
Tables
- TABLE 1
Clinical characteristics of study populations
All subjects Repeatability cohort Subjects n 84 20 Gender male:female 62:22 15:5 Age years 70±7.3 69±7 FEV1 % predicted 51±17 50±15 FEV1 L 1.36±0.53 1.35±0.43 FVC L 2.70±0.86 2.57±0.55 FEV1/FVC ratio 0.49±0.13 0.52±0.13 GOLD spirometry stage GOLD 1: 2 GOLD 1: 0 GOLD 2–3: 69 GOLD 2–3: 17 GOLD 4: 13 GOLD 4:3 CAT score 18.64±7.48 21.14±7.15 mMRC score 2.85±0.83 2.93±0.75 BMI kg·m−2 29±7 29±7 Smoker current:ex 9:75 1:19 Baseline characteristics presented as mean±sd unless otherwise stated. n=20. FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; GOLD: Global Initiative for Chronic Obstructive Lung Disease; CAT score: COPD Assessment Test score; mMRC: Modified Medical Research Council Dyspnoea Score; BMI: body mass index.
- TABLE 2
Intraclass correlation coefficients for within and between visit measures of the lung clearance index
Mean±sd V1 Mean±sd V2 Within visit ICC 20 min Mean±sd V3 (between visit) Between visit ICC 8 weeks FEV1 1.36±0.47 1.42±0.46 1.35±0.43 0.92 FEV1 % 51.45±14.86 52.94±16.71 52.94±16.71 0.92 FEF25–75 0.58±0.36 0.62±0.26 0.62±0.26 0.64 FVC L 2.58±0.63 2.86±0.73 2.57±0.55 0.74 LCI1/40th 11.24±2.25 11.11±1.90 0.92 11.42±2.03 0.88 FRC1/40th L 3.51±1.11 3.19±0.93 0.96 3.50±0.89 0.92 Scond 0.06±0.11 0.06±0.15 0.94 0.04±0.03 0.52 Sacin 0.784±0.46 0.84±0.59 0.95 0.698±0.40 0.80 LCIds 1.29±0.36 1.27±0.21 0.47 1.43±0.38 0.05 LCIvent 1.54±0.31 1.50±0.25 0.80 1.51±0.20 0.10 LCI1/20th 8.59±1.43 8.40±1.27 0.96 8.53±1.18 0.80 FRC1/20th L 3.40±1.05 3.55±1.01 0.90 3.38±1.01 0.91 n=19. Intraclass correlation coefficient (ICC) measured by Pearson's correlation coefficient. FEV1: forced expiratory volume in 1 s; FEF25–75: forced expiratory flow at at 25–75% of FVC; FVC: forced vital capacity; LCI: lung clearance index; FRC: functional residual capacity; Scond: convection-dependent ventilation heterogeneity, Sacin: diffusion-convection-dependent ventilation heterogeneity. 1/40th=FRC or LCI calculated at traditional stopping point. 1/20th=FRC or LCI calculated at truncated stopping point of 1/20th of the end tidal wash-in concentration over three consecutive breaths.
- TABLE 3
Sample size calculation for within and between visit (V) study designs
Change in LCI Within visit limits of agreement (V2-V1) Between visit limits of agreement (V3-V1) 80% power 90% power 80% power 90% power 2.4 15 19 12 16 2.6 12 16 10 13 2.8 11 14 9 12 3.0 9 12 8 10 Estimated sample size calculation using an absolute change in lung clearance index (LCI)1/40th and the within- and between-visit limits of agreement at 80% and 90% power.
- TABLE 4
One-way ANOVA for COPD GOLD staging
GOLD 1 GOLD 2 GOLD 3 GOLD 4 p-value Subjects n 2 38 25 14 LCI1/20th 7.89 8.14±1.02* 8.08±1.15 9.35±1.19* <0.01 LCI1/40th 10.01 10.46±1.6* 11.03±2.24 12.25±2.47* 0.05 Scond 0.02 0.06±0.09 0.06±0.11 −0.01±0.14 0.31 Sacin 0.40 0.35±0.28 0.46±0.37 0.61±0.41 0.16 One-Way ANOVA stratified by disease severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry strata. LCI: lung clearance index; Scond: conducting zone; Sacin: acinar zone. *: post hoc tests (Tukey's) between GOLD staging p<0.05.
- TABLE 5
Univariate correlation of LCI1/20th and physiological indices
LCI1/20th LCI1/40th LCI1/20th 0.76** LCI1/40th 0.76** FEV1 % predicted −0.40** −0.25* FVC % predicted −0.11 −0.61 FEF25–75 −0.43 −0.36 Scond −0.19 −0.07 Sacin 0.22 0.11 N=80. Pearson's correlation coefficient of lung clearance index (LCI), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow at at 25–75% of FVC (FEF25–75), and Phase III analysis of the conducting zone (Scond) and acinar zone (Sacin). *p<0.05; **p<0.01.
