Assessment of Ventilatory Heterogeneity in Chronic Obstructive Pulmonary Disease Using the Inspired Sinewave Test

Figures & data

Table 1 Participant Characteristics and Pulmonary Function Test Measurements

	COPD		Healthy
N	83		53
Male/Female	48/35		35/18
	Mean	SD	Mean	SD
Age (yrs)	67.35	9.91	64.69	11.64
Height (m)	1.69	0.09	1.70	0.12
Weight (kg)	78.35*	16.90	71.23	11.67
BMI	27.39*	5.30	23.77	4.11
FEV1 (L)	1.52*	0.64	3.28	0.99
FEV1% pred	55.08*	19.63	101.90	16.68
FVC (L)	3.12*	0.98	4.21	1.27
FVC % pred	84.53*	20.87	105.03	18.09
FEV1%FVC	48.46*	13.26	77.57	6.76
FEV1%FVC % pred	63.12*	18.26	96.56	7.25
TLC (L)	6.91*	1.61	6.16	1.38
TLC % pred	115.44*	20.41	100.68	20.85
RV (L)	3.59*	1.39	2.12	0.74
RV % pred	154.57*	51.87	101.70	21.52
FRC (L)	4.41*	1.47	3.39	0.84
FRC % pred	136.94*	40.21	106.86	17.37
TLCO	4.90*	1.72	7.90	2.52
TLCO % pred	60.54*	18.28	89.24	14.77
KCO	1.02*	0.29	1.49	0.30
KCO % pred	73.98*	22.09	96.22	16.10
Pack years	32.64	20.69	–	–
mMRC-DS	2.13	1.00	–	–
CAT	16.27	6.37	–	–

Note: *Statistically significant difference with healthy participants (P<0.05).

Abbreviations: SD, standard deviation; BMI, body mass index; PEF, peak expiratory flow; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; TLC, total lung capacity; RV, residual volume; FRC, functional residual capacity; T_LCO, transfer factor for carbon monoxide; K_CO, transfer coefficient for carbon monoxide; mMRC-DS, modified Medical Research Council dyspnoea scale, CAT; COPD assessment test; % predicted values obtained via reference values.^48,49

Figure 1 (A–D) Comparisons of (A) ELV₁₈₀/FRC_pleth, (B) ELV₁₈₀/ELV_pred, (C) ELV₆₀/ELV₁₈₀ and (D) FRC_pleth%pred in COPD patients (blue) and healthy participants (red). Long horizontal bar = mean; short horizontal bar = standard deviation; *Statistically significant difference (P<0.05). (E–H) scatterplots of (E) ELV₁₈₀/FRC_pleth, (F) ELV₁₈₀/ELV_pred, (G) ELV₆₀/ELV₁₈₀ and (H) FRC_pleth%pred vs FEV₁%pred in COPD patients with a linear regression line in D; r = +0.58 (P<0.05). For definitions see Table 1.

Figure 2 Receiver operator characteristic (ROC) curves for ELV₁₈₀/FRC_pleth, ELV₁₈₀/FRC_pleth % pred and ELV₁₈₀/ELV_pred. When it became apparent that specificity could be improved by normalising ELV₁₈₀/FRC_pleth for age, a ROC curve for the additional parameter ELV₁₈₀/FRC_pleth %pred was constructed.

Abbreviations: AUC, area under curve; SE, standard Error; YI, Youden’s index (maximal sensitivity+specifity-1).

Table 2 Univariable and Multivariable Linear Regression Analysis of ELV₁₈₀/FRC_pleth and ELV₁₈₀/ELV_pred as Predictors of Several Clinical Features (Dependent Variables) of COPD, Independent of FEV_1%pred

Dependent Variable	Independent Variable/s	Univariable Analysis		Multivariable Analysis
				ELV180/FRCpleth & FEV1%pred			ELV180/ELVpred & FEV1%pred
		R^2	P	R^2	Std Coeff	P	R^2	Std Coeff	P
CAT	FEV1%pred	0.12	0.001	0.28	−0.47	0.48	0.22	−0.314	0.002
	ELV180/FRCpleth	0.26	<0.001		−0.83	<0.001
	ELV180/ELVpred	0.13	0.001					−0.312	0.002
mMRC Dyspnoea Scale	FEV1%pred	0.06	0.028	0.27	0.08	0.5	0.12	−0.21	0.049
	ELV180/FRCpleth	0.26	<0.001		−0.56	<0.001
	ELV180/ELVpred	0.07	0.017					−0.23	0.03
Cough + Mucus Score	FEV1%pred	0.02	0.657	0.16	0.19	0.15	0.33	0.23	0.8
	ELV180/FRCpleth	0.13	0.05		−0.41	0.002
	ELV180/ELVpred	0.33	<0.001					−0.58	<0.001
TLCO %pred	FEV1%pred	0.13	<0.001	0.23	0.19	0.125	0.23	0.28	0.002
	ELV180/FRCpleth	0.25	<0.001		0.35	0.004
	ELV180/ELVpred	0.16	<0.001					0.35	0.001
%LAA	FEV1%pred	0.24	0.027	0.33	−0.31	0.227	0.32	−0.47	0.042
	ELV180/FRCpleth	0.25	0.024		−0.32	0.224
	ELV180/ELVpred	0.14	0.10					−0.33	0.091

Notes: Std Coeff, standardised regression coefficient (beta weight). This refers to the number of SDs the dependent variable will change per SD change of the independent variable. See Table 1, Figure 4 and/or methods for additional definitions.

Figure 3 Scatterplot of ELV₁₈₀ (L) vs FRC_pleth (L) with linear regression lines. Blue = COPD, Red = COPD. COPD, y = 0.19x + 0.59 (R² = 0.28); Healthy, y = 0.74x – 0.19 (R² = 0.64).

Figure 4 Scatterplots of ELV₁₈₀/FRC_pleth (A and B), ELV₁₈₀/ELV_pred (C and D) and FRC_pleth%pred (E and F) with T_LCO%pred and CT-derived morphological degree of emphysema (%LAA; low-attenuation area less than –950 Hounsfield units). See Table 1 for other definitions. Black linear regression lines are shown in A (r = +0.51), B (r = −0.5), C (r = +0.41), D (r = −0.37), and F (r = +0.33) respectively (P<0.05).

Figure 5 Scatterplots of ELV₁₈₀/FRC_pleth, ELV₁₈₀/ELV_pred and FRC_pleth%pred with the COPD assessment test (CAT), and dot plots of ELV₁₈₀/FRC_pleth, ELV₁₈₀/ELV_pred and FRC_pleth%pred and the modified Medical Research Council (mMRC) dyspnoea scale and a cough + mucus score derived from the first two question of the CAT (see methods for further details). Scatterplots (A, D and G) include a linear regression line, r = −0.52, r = −0.36 and r = +0.36, respectively (P<0.05). *Statistically significant difference (P<0.05) from mMRC Dyspnoea score = 0/1 (B, E and H) or Cough + Mucus score = 0–3 (C, F and I). ^†Statistical significant difference (P<0.05) from mMRC Dyspnoea score = 2 (B and E) or Cough + Mucus score = 4–5 (C and F).

Figure 6 (A) Scatterplot of ELV₁₈₀/ELV_pred vs FRC_%pred for COPD patients. Patient data has been additionally categorised into quadrants (“COPD phenotype” I–IV) using the conventionally accepted threshold of lung hyperinflation (FRC_pleth%pred = 120%),²⁸ and the lower boundary of normality for ELV₁₈₀/ELV_pred (ie, 2 Z-scores below mean ELV₁₈₀/ELV_pred in healthy participants ≈ 0.7)/Quadrant I, FRC_%pleth <120% and ELV₁₈₀/ELV_pred ≥ 0.7; II, FRC_%pleth <120% and ELV₁₈₀/ELV_pred < 0.7; III, FRC_%pleth ≥120% and ELV₁₈₀/ELV_pred ≥ 0.7; IV, FRC_%pleth ≥120% and ELV₁₈₀/ELV_pred < 0.7. See Figure 5 and text for further details. (B–D) Bar charts of the mean (±SD) CAT, mMRC Dyspnoea, and Cough + Mucus scores for each phenotype (I–IV). *Statistical significant difference (P<0.05) from COPD phenotype III. ^†Statistical significant difference (P<0.05) from COPD phenotype II. ^‡Near statistical difference (P=0.09) with COPD phenotype IV.

Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault J-C. Lung volumes and forced ventilatory flows. Eur Respir J. 1993;6(Suppl 16):5–40. doi:10.1183/09041950.005s1693

 PubMed Web of Science ®Google Scholar

Quanjer PH, Stanojevic S, Cole TJ, et al. Multi-ethnic reference values for spirometry for the 3–95 year age range: the global lung function 2012 equations. Eur Respir J. 2012;40:1324–1343. doi:10.1183/09031936.00080312

 PubMed Web of Science ®Google Scholar

O’Donnell DE, Laveneziana P. Physiology and consequences of lung hyperinflation in COPD. Eur Respir Rev. 2006;15(100):61–67. doi:10.1183/09059180.00010002

 Google Scholar