Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

Figures & data

Table 1 Characteristics of the 100 participants with COPD

Characteristics	All participants (n=100)	Group 1 (n=20)	Group 2 (n=80)
Age (years)	68±10	61±11	69±9**
Sex (F/M)	20/80	5/15	15/65
BMI (kg/m^2)	27±4	25±5	27±4
Smoking (pack-years)	44±27	40±17	44±30
CAT <10/≥10	47/53	19/1	28/52**
TLC (% of pred)	113±16	114±15	113±17
RV (% of pred)	152±42	138±26	156±45
RV/TLC (%)	52±12	45±8	54±12**
FEV1 (% of pred)	55±21	71±20	50±19**
FVC (% of pred)	78±21	94±20	74±20**
FEV1/FVC (%)	53±10	59±7	52±10**
FEF25–75 (% pred)	22±15	27±19	20±13
R5 – R20 (kPa·s·L^−1)	0.176±0.136	0.013±0.016	0.216±0.122**
R5 (kPa·s·L^−1)	0.532±0.192	0.334±0.098	0.581±0.178**
R20 (kPa·s·L^−1)	0.356±0.084	0.323±0.095	0.363±0.081
X5 (kPa·s·L^−1)	−0.255±0.154	−0.099±0.049	−0.294±0.147**
AX (kPa·L^−1)	2.288±1.991	0.245±0.192	2.799±1.908**
FRes (Hz)	22.17±8.1	11.51±3.2	24.83±6.7**
ΔFVC (%)	5.10±8.5	1.72±5.8	5.95±8.8*
ΔFEV1 (%)	6.47±8.6	4.04±8.7	7.08±8.5

Notes: Group 1: participants with R5 – R20 ≤0.030 kPa·s·L⁻¹; Group 2: participants with R5 – R20 >0.030 kPa·s·L⁻¹. The values presented in this table refer to measurements made before bronchodilation. Values are expressed as mean ± SD or as the ratio. Comparisons between mean ± SD values and between ratio values were analyzed by the unpaired t-test and Pearson’s χ² test, respectively.

* P<0.05;

** P<0.01.

Abbreviations: AX, area of low-frequency reactance; BMI, body mass index; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; F, female; FEF25–75, forced expiratory flow in the middle half of the patient’s exhaled volume; FEV₁, forced expiratory volume in 1 second; F_Res, resonant frequency; FVC, forced vital capacity; M, male; pred, predicted; R5, resistance at 5 Hz; R20, resistance at 20 Hz; R5 – R20, fall in resistance from 5 Hz to 20 Hz; RV, residual volume; SD, standard deviation; TLC, total lung capacity; X5, reactance at 5 Hz; ΔFVC, the percentage change relative to the prebronchodilator value of FVC; ΔFEV₁, the percentage change relative to the prebronchodilator value of FEV₁.

Table 2 Correlations between IOS (R5 – R20, X5, AX, and F_Res) and spirometric and plethysmographic (FEF25–75, RV, and RV/TLC) measures of small airway obstruction in 100 participants with COPD

	R5 – R20	X5	AX	FRes	FEF25–75	RV
X5	r=−0.928, P<0.01
AX	r=−0.970, P<0.01	r=−0.947, P<0.01
FRes	r=−0.886, P<0.01	r=−0.812, P<0.01	r=0.907, P<0.01
FEF25–75	r=−0.364, P<0.01	r=0.394, P<0.01	r=−0.386, P<0.01	r=−0.421, P<0.01
RV	r=0.408, P<0.01	r=−0.415, P<0.01	r=0.475, P<0.01	r=0.485, P<0.01	r=−0.422, P<0.01
RV/TLC	r=0.556, P<0.01	r=−0.612, P<0.01	r=0.597, P<0.01	r=0.600, P<0.01	r=−0.566, P<0.01	r=0.782, P<0.01

Note: r, Pearson’s correlation coefficient.

Abbreviations: AX, area of low-frequency reactance; COPD, chronic obstructive pulmonary disease; FEF_25–75, forced expiratory flow in the middle half of the patient’s exhaled volume; F_Res, resonant frequency; IOS, impulse oscillometry system; R5 – R20, fall in resistance from 5 Hz to 20 Hz; RV, residual volume; TLC, total lung capacity; X5, reactance at 5 Hz.

Figure 1 Relationship between ΔFVC and ΔFEV₁ in 100 participants with COPD (r=0.573, P<0.01; r= Pearson’s correlation coefficient).

Notes: Group 1: participants with R5 – R20 ≤0.030 kPa·s·L⁻¹; Group 2 participants with R5 – R20 >0.030 kPa·s·L⁻¹. When participants were divided according to the median value of ΔFVC of the entire population of participants (interrupted vertical line), 45 out of 80 participants of Group 2 and 5 out of 20 participants of Group 1 had a ΔFVC value higher than the median value (χ²=6.250, P=0.012). By contrast, 40 out of 80 participants of Group 2 and 10 out of 20 participants of Group 1 had a ΔFEV₁ value higher than the median value of ΔFEV₁ (interrupted horizontal line) (χ²=0.0, P=1.0).

Abbreviations: COPD, chronic obstructive pulmonary disease; R5 – R20, fall in resistance from 5 Hz to 20 Hz; ΔFVC, the percentage change relative to prebronchodilator value of forced vital capacity; ΔFEV₁, the percentage change relative to prebronchodilator value of FEV₁.

Figure 2 Relationship between ΔFVC and R5 – R20 in 100 participants with COPD.

Abbreviations: COPD, chronic obstructive pulmonary disease; R5 – R20, fall in resistance from 5 Hz to 20 Hz; ΔFVC, the percentage change relative to prebronchodilator value of forced vital capacity.

Table 3 Spirometric, plethysmographic, and IOS data of nonresponders and the three groups of responders

	Nonresponders (n=69)	Volume responders (n=16)	Flow responders (n=8)	Volume and flow responders (n=7)
TLC (% of pred)	113±15	115±22	109±11	115±14
RV (% of pred)	148±42	174±39	129±33	170±49
RV/TLC (%)	50±11	61±7#	44±12	56±10
FEV1 (% of pred)	58±21	37±16#	62±15	52±13
FVC (% of pred)	81±21	63±19#	87±15	72±14
FEV1/FVC (%)	55±10	45±8¶	55±7	55±8
FEF25–75 (% pred)	24±16	13±9¶	23±11	19±10
R5 – R20 (kPa·s·L^−1)	0.145±0.128	0.294±0.115#	0.106±0.079	0.291±0.090#
R5 (kPa·s·L^−1)	0.490±0.187	0.684±0.153#	0.449±0.103	0.694±0.130#
R20 (kPa·s·L^−1)	0.344±0.087	0.389±0.088	0.342±0.063	0.401±0.049
X5 (kPa·s·L^−1)	−0.220±0.147	−0.396±0.127#	−0.187±0.086	−0.363±0.124
AX (kPa·L^−1)	1.792±1.74	4.277±1.98#	1.295±1.16	3.773±1.48
FRes (Hz)	20.35±7.7	29.31±7.01#	19.32±7.01	27.12±5.37

Notes: The values presented in this table refer to measurements made before bronchodilation. Values are expressed as mean ± SD.

# P<0.05 vs nonresponders and flow responders;

¶ P<0.05 vs nonresponders by means of ANOVA and post hoc test.

Abbreviations: ANOVA, analysis of variance; AX, area of low-frequency reactance; FEF_25–75, forced expiratory flow in the middle half of the patient’s exhaled volume; FEV₁, forced expiratory volume in 1 second; F_Res, resonant frequency; FVC, forced vital capacity; IOS, impulse oscillometry system; pred, predicted; R5, resistance at 5 Hz; R20, resistance at 20 Hz; R5 – R20, fall in resistance from 5 Hz to 20 Hz; RV, residual volume; SD, standard deviation; TLC, total lung capacity; X5, reactance at 5 Hz.