Factors for the Variability of Three Acceptable Maximal Expiratory Flow–Volume Curves in Chronic Obstructive Pulmonary Disease

Figures & data

Table 1 Characteristics of the Participants

Characteristics			Overall (n=85)
Age, years			72.4 (8.3)
Gender (male/female)			78/7
BMI (kg/m^2)			22.4 (0.3)
Smoking, pack-years			65.4 (28.5)
Current smoker, N (%)			12 (14.1)
Clinical symptoms
Chronic cough, N (%)			13 (15.3)
Chronic sputum, N (%)			19 (22.4)
The frequency of wheeze^a A/B/C, N			52/23/10
Lung function
Pre-bronchodilator
FEV1, L			1.42 (1.05–2.04)
FEV1, % predicted			60.0 (43.4–80.8)
FVC, % predicted			107.7 (91.1–119.5)
FEV1/FVC, %			46.5 (36.2–57.3)
KCO, % predicted			68.2 (55.0–86.1)
Post-bronchodilator
FEV1, L			1.61 (1.21–2.18)
FEV1, % predicted			65.3 (51.2–85.7)
FVC, % predicted			113.1 (97.5–126.0)
FEV1/FVC, %			47.8 (37.9–59.8)
Reversibility, N (%)			17 (20.0)
GOLD stage^b 1/2/3/4, N			28/36/18/3
Blood analysis
Serum total IgE (log cells/µL)			1.80 (0.07)
Peripheral eosinophils (log cells/µL)			2.22 (0.03)
LAV, % total lung volume			24.3 (14.9–39.4)

Notes: Data with normal distribution were presented as mean (SD), and data with skewed distribution were expressed as median (IQR). Data on the frequency of wheezing^a were obtained via interview within the last 6 months prior to the examination day: group A: none, B: only 2–3 days/month, and C: few days/weeks to almost every day. GOLD stage^b 1 was defined as predicted FEV₁/FVC ratio <70% and predicted FEV₁ >80%. GOLD stage 2 was defined as predicted FEV₁/FVC ratio between 70% and 50% and predicted FEV₁ ≤ 80%. GOLD stage 3 was defined as predicted FEV₁/FVC ratio between 70% and 30% and predicted FEV₁ ≤ 50%. GOLD stage 4 was defined as predicted FEV₁/FVC ratio <70% and predicted FEV₁ ≤ 30% or < 50% plus chronic respiratory failure.

Abbreviations: BMI, body mass index; BD, bronchodilator; FVC, forced expiratory capacity; FEV₁, forced expiratory volume in 1 s; K_CO, Krogh’s constant for CO (DL_CO/V_A); DL_CO, diffusing capacity of the lungs for carbon monoxide; V_A, alveolar volume; GOLD, Global Initiative for Chronic Obstructive Lung Disease; Ig, immunoglobulin; LAV, low attenuation volume.

Figure 1 Differences in coefficient of variations (CVs) for the parameters of flow–volume curves in 85 participants with COPD. Based on the three best maneuvers, the median (IRQ) CV for FVC (1.6% [range: 0.9–2.2%] or FEV₁ (2.0% [range: 1.0–3.0%], p < 0.0001) were significantly lower than the PEF, FEF₅₀, and FEF₇₅ (5.0% [range: 3.3–6.8%), p < 0.0001; 5.6% (range: 3.9–8.4%), p < 0.0001; and 6.9% (range: 5.1–10.8), p < 0.0001, respectively). This result indicated that FVC or FEV₁ had consistent values in spirometry even in participants with COPD. Data were presented as median (IRQ) (†p < 0.0001).

Table 2 Relationships Between Variability in FVC or FEV₁ (Log CV for FVC or FEV₁) as Well as Demographic Characteristics, Clinical Symptoms, PFT Findings, Blood Analysis Results, and CT Scan Variables

Variables	Statistical Test		No		FVC (Log CV, %)				FEV1 (Log CV, %)
					Mean (SD)	Statistic	p value		Mean (SD)	Statistic	p value
Sex	Unpaired t-test	Male	78		0.147 (0.290)		0.681		0.247 (0.351)		0.531
		Female	7		0.099 (0.342)				0.199 (0.342)
Age	Pearson correlation		85			0.261	0.016			0.381	<0.0001
BMI	Pearson correlation		85			−0.047	0.67			−0.074	0.5
Smoking status	Unpaired t-test	Former	72		0.122 (0.298)		0.96		0.232 (0.358)		0.226
		Current	13		0.274 (0.223)				0.308 (0.295)
Chronic cough	Unpaired t-test	+	13		0.247 (0.245)		0.163		0.298 (0.349)		0.673
		-	72		0.124 (0.298)				0.233 (0.351)
Chronic sputum	Unpaired t-test	+	19		0.119 (0.304)		0.162		0.295 (0.353)		0.81
		-	66		0.226 (0.238)				0.228 (0.349)
Frequency of wheezing^a	Kruskal–Wallis test	A B	52 23		0.122 (0.287) 0.127 (0.322)		0.301		0.167 (0.349) 0.320 (0.305)		0.034
		C	10		0.289 (0.231)				0.460 (0.346)
Pre-BD FEV1 (% predicted)	Pearson correlation		85			−0.293	0.007			−0.34	<0.0001
Reversibility	Unpaired t-test	+	17		0.165 (0.256)		0.738		0.466 (0.190)		0.004
		-	68		0.137 (0.302)				0.187 (0.358)
Serum total IgE (log)	Pearson correlation		85			0.169	0.132			−0.084	0.453
Peripheral eosinophils (log)	Pearson correlation		85			0.055	0.618			0.054	0.624
%LAV	Pearson correlation		85			−0.083	0.453			−0.85	0.44

Notes: Data on the frequency of wheezing^a were obtained via interview within the last 6 months prior to the examination day: group A: none, B: only 2–3 days/month, and C: few days/weeks to almost every day.

Abbreviations: CV, coefficient of variation; FVC, forced expiratory capacity; FEV_1, forced expiratory volume in 1 s; BMI, body mass index; BD, bronchodilator; Ig, immunoglobulin; LAV, low attenuation volume.

Figure 2 Differences in CVs for FVC or FEV₁ according to COPD stage based on the GOLD criteria and age. (A) The median CV for FVC in stage 3 or 4 COPD (1.9% [range: 1.2–2.8%]) significantly varied compared with that in stage 1 COPD (1.2% [range: 0.7–1.6%], p = 0.01). In addition, stage 2 COPD (1.7% [range:1.2–2.3%]) significantly varied compared with stage 1 COPD (p = 0.008). (B) The median CV for FVC in the oldest group (aged 71–80 years; 1.7% [range: 0.9–2.3%]) significantly varied compared with the youngest group (1.1% [range: 0.6–1.5%], p = 0.049). (C) The median CV for FEV₁ in stage 3 or 4 COPD (2.5% [range:1.7–5.4%]) significantly varied compared with that in stage 1 COPD (1.1% [range: 0.8–2.0%], p = 0.001) and stage 2 COPD (2.4% [range: 1.2–3.4%], p = 0.003). (D) The median CV for FEV₁ in the oldest group (aged 81–90 years; 1.8% [range:1.8–6.0%]) significantly varied compared with the other groups (1.6% [range: 0.9–2.0%], p = 0.043; 1.6% [range: 0.8–2.3%], p = 0.003; and 2.0% [range: 1.1–3.1%], p = 0.046). Data were presented as median (IRQ).

Table 3 Results of the Stepwise Analysis on the Correlation Coefficient for the Intra-Individual Variability in FVC and FEV₁

Variables	Coefficient	p value
FVC (Log CV, %)
pre-BD %FEV1	−0.335	0.005
FEV1 (Log CV, %)
Age	0.238	0.008
pre-BD %FEV1	−0.377	0.001
%LAV	−0.28	0.006

Abbreviations: CV, coefficient of variation; FVC, forced expiratory capacity; BD, bronchodilator; FEV₁, forced expiratory volume in 1 s; LAV, low attenuation volume.

Table 4 dFEV₁ in the Different Stages of COPD

	Stage 1	Stage 2	Stage 3 or 4
No	28	36	21
Number of dFEV1 is over 100mL, N (%)	6 (21.4%)	6 (16.7%)	2 (9.5%)
dFEV1, mL	60.7 ± 35.6	59.2 ± 36.5	48.1 ± 32.5