Area under the forced expiratory flow-volume loop in spirometry indicates severe hyperinflation in COPD patients

Figures & data

Figure 1 Area under the forced expiratory FVL is determined by integrating all flow-volume measurement points of the observed FVL.

Note: AreaFE% is obtained by expressing AreaFE as a percentage of the reference area, which is determined from the reference FVL estimated using predicted values of FVC, PEF, FEF25, FEF50 and FEF75.
Abbreviations: AreaFE%, area under the forced expiratory flow-volume loop expressed as a percentage of the reference value; FEFx, forced expiratory flow at x (25%, 50% or 75%) of FVC; FVL, flow-volume loop; PEF, peak expiratory flow; pred, predicted values.

Figure 2 Presence of severe static hyperinflation (shown in black) in cohort A (n=215) according to (A) RV/TLC >60% and (B) IC/TLC <25% across all GOLD stages.

Note: No patient in GOLD I and more than 80% patients in GOLD IV had severe hyperinflation according to both criteria.

Abbreviations: IC, inspiratory capacity measured using body plethysmography; RV, residual volume; TLC, total lung capacity.

Figure 3 Distribution of AreaFE% in each GOLD stage is shown: it decreases significantly with airflow obstruction severity from GOLD I to GOLD IV (P<0.0001).

Abbreviation: AreaFE%, area under the forced expiratory flow-volume loop expressed as a percentage of the reference value.

Table 1 Baseline characteristics of cohort A (n=215)

	GOLD I	GOLD II	GOLD III	GOLD IV
Patients (n)	42	65	52	56
Gender (male/female)	36/6	53/12	41/11	34/22
Age (years)	64±6	66±9	67±7	60±7
Height (cm)	173±8	169±8	169±8	166±8
Smoking (pack-years)	47±22	56±31	53±23	40±26
FEV1%	88±10	60±12	36±5	27±6
FEV1/FVC (%)	62±5	51±9	37±8	27±6
RV/TLC (%)	38±7	48±7	60±7	68±8
IC/TLC (%)	42±6	33±7	23±5	17±5
Raw%	155±52	217±76	285±85	354±89
DLCO%	75±18	61±18	38±14	32±10
AreaFE%	79±18	37±13	15±4	7±3

Note: Values are mean ± SD.

Abbreviations: AreaFE%, area under the forced expiratory flow-volume loop expressed as a percentage of the reference value; DLCO, diffusion capacity of the lungs for carbon monoxide; IC, inspiratory capacity measured using body plethysmography; Raw, airway resistance; RV, residual volume; TLC, total lung capacity.

Table 2 Correlations of AreaFE% and conventional spirometry parameters with RV/TLC and IC/TLC in sub-cohort A (GOLD II, III and IV subjects from cohort A, n=173)

Parameters	r (RV/TLC)	r (IC/TLC)
AreaFE%	−0.78	0.8
FEV1%	−0.79	0.8
FVC%	−0.74	0.49
FEV1/FVC%	−0.55	0.73
PEF%	−0.73	0.72
FEF25%–75%	−0.64	0.73
ICs%	−0.74	0.71

Note: All correlations were statistically significant (P<0.01).

Abbreviations: AreaFE%, area under the forced expiratory flow-volume loop expressed as a percentage of the reference value; FEF25%–75%, forced expiratory flow between 25% and 75% of FVC expressed as a percentage of the reference value; IC, inspiratory capacity measured using body plethysmography; IC_s, inspiratory capacity measured during spirometry; PEF%, peak expiratory flow expressed as a percentage of the reference value; RV, residual volume; TLC, total lung capacity.

Figure 4 Distribution of the area under the forced expiratory flow-volume loop expressed as a percentage of the reference value (AreaFE%) in sub-cohort A (GOLD II, III and IV subjects from cohort A, n=173) shown against (A) RV/TLC and (B) IC/TLC.

Note: The cut-offs for AreaFE% indicating severe hyperinflation using RV/TLC >60% and IC/TLC <25% were determined at 13% and 17%, respectively, from ROC analysis.
Abbreviations: AreaFE%, area under the forced expiratory flow-volume loop expressed as a percentage of the reference value; IC, inspiratory capacity measured using body plethysmography; ROC, receiver operating characteristics; RV, residual volume; TLC, total lung capacity.

Table 3 ROC cut-offs developed in sub-cohort A (GOLD II, III and IV subjects from cohort A, n=173) and validation in sub-cohort B (GOLD II, III and IV subjects from cohort B, n=75)

	Parameters	Training (n=173)		Validation (n=73)
		Cut-off (%)	Accuracy (%)	Sensitivity (%)	Specificity (%)
RV/TLC > ULN	AreaFE%	23	81	75	81
	FEV1%	48	72	75	69
	FVC%	89	65	62	69
	FEV1/FVC%	42	57	58	56
	PEF%	52	65	62	69
	FEF25%–75%	13	70	62	81
	ICs%	57	70	75	62
RV/TLC >60%	AreaFE%	13	80	68	83
	FEV1%	34	73	64	79
	FVC%	75	75	61	83
	FEV1/FVC%	38	65	68	64
	PEF%	41	71	61	77
	FEF25%–75%	9	71	50	83
	ICs%	51	69	68	70
IC/TLC <25%	AreaFE%	17	80	75	79
	FEV1%	38	75	69	79
	FVC%	78	60	50	69
	FEV1/FVC%	38	76	75	77
	PEF%	45	73	69	77
	FEF25%–75%	11	77	72	82
	ICs%	55	69	75	64

Abbreviations: AreaFE%, area under the forced expiratory flow-volume loop expressed as a percentage of the reference value; FEF25%–75%, forced expiratory flow between 25% and 75% of FVC expressed as a percentage of the reference value; IC, inspiratory capacity measured using body plethysmography; IC_s, inspiratory capacity measured during spirometry; PEF%, peak expiratory flow expressed as a percentage of the reference value; ROC, receiver operating characteristics; RV, residual volume; TLC, total lung capacity; ULN, upper limit of normal.

Figure 5 Bland–Altman plots showing (A) the difference of 100-AreaFE% and RV/TLC against their mean and (B) the difference of AreaFE% and IC/TLC against their mean.

Note: The biases are determined at 21.4% and −4%, respectively, but with a similar width of ~39% between the limits of agreement.
Abbreviations: AreaFE%, area under the forced expiratory flow-volume loop expressed as a percentage of the reference; IC, inspiratory capacity measured using body plethysmography; RV, residual volume; TLC, total lung capacity.