Impact of exacerbations on respiratory system impedance measured by a forced oscillation technique in COPD: a prospective observational study

Figures & data

Table 1 Characteristics of subjects at enrollment

	N=51
Observation period (months)	57 (52–59)
Age (years)	72 (64–76)
Sex (male/female)	43/8
Body mass index (kg/m^2)	20.9 (18.8–23.0)
Smoking state (current/ex)	11/40
Smoking (pack-year)	45 (30–70)
GOLD stage (1/2/3/4)	2/30/18/1
Medication for COPD
Any medications	47
LAMA	47
ICS + LABA	19
COPD assessment test score	6 (3–10)
Neutrophils (/µL)	3,602 (3,130–4,295)
Eosinophils (/µL)	156 (98.3–231)
IgE (IU/mL)	78 (18–173)
FeNO (ppb)	15 (11–20)

Notes: Values are shown as the median (25%–75%). Neutrophils, eosinophils, and IgE were measured in blood.

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; LAMA, long-acting muscarinic antagonist; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; IgE, immunoglobulin E; FeNO, fractional exhaled nitric oxide; ppb, parts per billion.

Table 2 Respiratory system impedance and FEV₁ at enrollment

	N=51
R5 (cmH2O/L/s)
Whole breath	3.52 (2.51–4.02)
Inspiratory	3.20 (2.29–3.67)
Expiratory	3.62 (2.68–4.23)
⊿R5	0.42 (0.18–0.8)
R20 (cmH2O/L/s)
Whole breath	2.54 (2.14–2.98)
Inspiratory	2.28 (1.80–2.65)
Expiratory	2.62 (2.25–3.23)
⊿R20	0.22 (0.11–0.44)
R5–R20 (cmH2O/L/s)
Whole breath	1.14 (0.51–1.51)
Inspiratory	0.98 (0.27–1.56)
Expiratory	0.91 (0.22–1.49)
⊿R5–R20	0.30 (0.10–0.65)
X5 (cmH2O/L/s)
Whole breath	−1.14 (−2.02 to −0.70)
Inspiratory	−0.82 (−1.60 to −0.56)
Expiratory	−1.27 (−2.10 to −0.59)
⊿X5	−0.36 (−1.00 to −0.11)
Fres (Hz)
Whole breath	12.35 (8.51–15.13)
Inspiratory	11.13 (8.14–14.52)
Expiratory	12.99 (8.95–16.62)
⊿Fres	1.00 (−0.05–2.79)
FEV1 (L)	1.38 (0.95–1.80)

Notes: Values are shown as the median (25%–75%). ⊿, difference between inspiratory and expiratory phases.

Abbreviations: FEV₁, forced expiratory volume in 1 second; R5, respiratory system resistance at 5 Hz; R20, respiratory system resistance at 20 Hz; X5, respiratory system reactance at 5 Hz; Fres, resonant frequency.

Table 3 Annual changes of respiratory system impedance and FEV₁

	Annual change
R5 (cmH2O/L/s)
Whole breath	0.055 (−0.144–0.227)
Inspiratory	0.039 (−0.101–0.190)
Expiratory	0.024 (−0.169–0.251)
⊿R5	0.007 (−0.078–0.056)
R20 (cmH2O/L/s)
Whole breath	0.058 (−0.030–0.143)
Inspiratory	−0.006 (−0.179–0.139)
Expiratory	0.039 (−0.213–0.196)
⊿R20	−0.005 (−0.049–0.053)
R5–R20 (cmH2O/L/s)
Whole breath	0.013 (−0.162–0.191)
Inspiratory	−0.036 (−0.172–0.216)
Expiratory	0.014 (−0.171–0.138)
⊿R5–R20	0.024 (−0.068–0.075)
X5 (cmH2O/L/s)
Whole breath	−0.087 (−0.231 to −0.005)
Inspiratory	−0.075 (−0.172 to −0.017)
Expiratory	−0.110 (−0.309–0.011)
⊿X5	−0.050 (−0.156–0.068)
Fres (Hz)
Whole breath	0.733 (0.340–1.140)
Inspiratory	0.510 (0.317–1.045)
Expiratory	0.747 (0.222–1.259)
⊿Fres	0.105 (−0.233–0.558)
FEV1(mL)	−24.6 (−55.2–4.4)

Notes: Values are shown as the median (25%–75%). ⊿, difference between inspiratory and expiratory phases.

Abbreviations: FEV₁, forced expiratory volume in 1 second; R5, respiratory system resistance at 5 Hz; R20, respiratory system resistance at 20 Hz; X5, respiratory system reactance at 5 Hz; Fres, resonant frequency.

Table 4 Characteristics of subjects with and without exacerbations at enrollment

	Exacerbation	Nonexacerbation	P-value
Subjects (n)	25	26
Sex (male/female)	24/1	19/7
Age (years)	72.0 (66.5–74.5)	71.5 (61.8–78.5)	0.92
Smoking history (pack-year)	45 (25–65)	47.5 (30–65)	0.29
Smoking of recruitment	15 (60%)	12 (46%)
BMI (kg/m^2)	23.5 (20.4–25.8)	21.8 (20.4–23.8)	0.18
COPD assessment test score	6 (3–10)	6 (4–10)	0.69
GOLD stage (1/2/3/4)	1/14/10/0	1/16/8/1
Exacerbation in last year	*1 (1–1)	0 (0–1)	<0.01
Exacerbation during observation period	0.44 (0.23–0.63)	0 (0–0)
Neutrophils (/µL)	3,495 (2,960–3,907)	3,708 (3,264–4,873)	0.06
Eosinophils (/µL)	148 (58–223)	176 (50–218)	0.75
IgE (IU/mL)	54 (13–108)	95 (23–123)	0.52
FeNO (ppb)	15 (11–19)	15 (12–23)	0.47

Notes: Values are shown as the median (25%–75%).

* P<0.05. Neutrophils, eosinophils, and IgE were measured in blood.

Abbreviations: BMI, body mass index; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IgE, immunoglobulin E; FeNO, fractional exhaled nitric oxide; ppb, parts per billion.

Table 5 Respiratory system impedance and FEV₁ of subjects with and without exacerbations at enrollment

	Exacerbation	Nonexacerbation	P-value
Subjects (n)	25	26
R5 (cmH2O/L/s)
Whole breath	3.29 (2.09–3.78)	3.66 (3.11–4.20)	0.06
Inspiratory	3.02 (1.95–3.57)	3.35 (2.88–4.12)	0.06
Expiratory	3.56 (2.13–4.26)	3.74 (3.29–4.33)	0.21
⊿R5	0.40 (0.20–0.80)	0.44 (0.17–1.00)	0.95
R20 (cmH2O/L/s)
Whole breath	2.54 (2.15–2.99)	2.54 (2.09–2.98)	0.44
Inspiratory	2.44 (2.09–2.79)	2.10 (1.71–2.54)	0.16
Expiratory	2.64 (2.28–3.30)	2.60 (2.25–3.22)	0.87
⊿R20	0.18 (0.06–0.34)	0.23 (0.11–0.44)	0.28
R5–R20 (cmH2O/L/s)
Whole breath	0.93 (0.43–1.58)	1.15 (0.68–1.47)	0.37
Inspiratory	0.78 (0.21–1.76)	1.29 (0.48–1.56)	0.06
Expiratory	0.86 (0.17–1.51)	1.06 (0.42–1.31)	0.74
⊿R5–R20	0.37 (0.16–0.96)	0.20 (0.04–0.51)	0.25
X5 (cmH2O/L/s)
Whole breath	−0.96 (−1.62 to −0.57)	−1.20 (−2.58 to −0.80)	0.08
Inspiratory	−0.69 (−1.33 to −0.43)	−0.80 (−1.76 to −0.65)	0.14
Expiratory	−0.97 (−2.05 to −0.50)	−1.35 (−2.38 to −0.79)	0.09
⊿X5	−0.24 (−0.62 to −0.08)	−0.52 (−1.68–0.10)	0.30
Fres (Hz)
Whole breath	12.02 (8.86–14.75)	12.51 (10.45–16.30)	0.22
Inspiratory	11.04 (8.59–14.06)	11.70 (8.82–13.89)	0.74
Expiratory	12.51 (8.87–16.41)	13.36 (10.74–16.61)	0.29
⊿Fres	1.03 (0.21–2.43)	0.99 (−0.46–3.70)	0.81
FEV1(L)	1.40 (0.98–1.84)	1.31 (0.95–1.70)	0.60

Note: Values are shown as the median (25%–75%). ⊿, difference between inspiratory and expiratory phases.

Abbreviations: FEV₁, forced expiratory volume in 1 second; R5, respiratory system resistance at 5 Hz; R20, respiratory system resistance at 20 Hz; X5, respiratory system reactance at 5 Hz; Fres, resonant frequency.

Table 6 Annual changes of respiratory system impedance and FEV₁ of subjects with and without exacerbations at enrollment

	Exacerbation	Nonexacerbation	P-value
Subjects (n)	25	26
R5 (cmH2O/L/s)
Whole breath	*0.188 (0.056–0.310)	−0.037 (−0.170–0.103)	<0.01
Inspiratory	*0.146 (0.052–0.268)	−0.039 (−0.145–0.081)	<0.01
Expiratory	*0.187 (0.019–0.360)	−0.021 (−0.128–0.124)	<0.01
⊿R5	0.010 (−0.048–0.095)	−0.003 (−0.085–0.053)	0.40
R20 (cmH2O/L/s)
Whole breath	0.048 (−0.041–0.159)	−0.065 (−0.025–0.124)	0.52
Inspiratory	0.047 (−0.114–0.163)	−0.105 (−0.216–0.151)	0.20
Expiratory	0.044 (−0.117–0.155)	−0.073 (−0.278–0.215)	0.34
⊿R20	0.001 (−0.065–0.067)	−0.018 (−0.049–0.038)	0.45
R5–R20 (cmH2O/L/s)
Whole breath	0.041 (−0.076–0.232)	−0.093 (−0.229–0.114)	0.07
Inspiratory	*0.050 (−0.101–0.294)	−0.152 (−0.183–0.142)	0.02
Expiratory	0.060 (−0.146–0.234)	−0.053 (−0.211–0.096)	0.10
⊿R5–R20	−0.006 (−0.134–0.076)	0.028 (−0.055–0.070)	0.56
X5 (cmH2O/L/s)
Whole breath	*−0.183 (−0.258 to −0.099)	−0.017 (−0.092–0.016)	<0.01
Inspiratory	*−0.103 (−0.212 to −0.056)	−0.049 (−0.127 to −0.023)	0.03
Expiratory	*−0.257 (−0.309 to −0.067)	0.006 (−0.140–0.092)	<0.01
⊿X5	*−0.121 (−0.228 to −0.012)	−0.004 (−0.073–0.148)	<0.01
Fres (Hz)
Whole breath	*1.044 (0.669–1.434)	0.266 (−0.022–0.767)	<0.01
Inspiratory	*0.891 (0.392–1.185)	0.410 (0.142–0.556)	<0.01
Expiratory	*1.013 (0.632–1.384)	0.293 (−0.029–0.839)	<0.01
⊿Fres	0.239 (−0.289–0.662)	0.014 (−0.198–0.553)	0.26
FEV1 (mL)	*−38.6 (−79.3–5.8)	−14.2 (−31.7–12.2)	<0.01

Notes: Values are shown as the median (25%–75%).

* P<0.05. ⊿, difference between inspiratory and expiratory phases.

Abbreviations: FEV₁, forced expiratory volume in 1 second; R5, respiratory system resistance at 5 Hz; R20, respiratory system resistance at 20 Hz; X5, respiratory system reactance at 5 Hz; Fres, resonant frequency.

Figure 1 The percentage of the annual change to baseline.

Note: The ratio of annual changes in respiratory system impedance, especially in X5 and Fres, was more apparent than that of FEV₁.

Abbreviations: R5, respiratory system resistance at 5 Hz; R20, respiratory system resistance at 20 Hz; X5, respiratory system reactance at 5 Hz; Fres, resonant frequency; FEV₁, forced expiratory volume in 1 second.

Figure 2 The percentage of the annual change to baseline in subjects with and without exacerbations.

Note: The ratio of X5 and Fres was remarkably greater in subjects with exacerbations than in those without.
Abbreviations: R5, respiratory system resistance at 5 Hz; R20, respiratory system resistance at 20 Hz; X5, respiratory system reactance at 5 Hz; Fres, resonant frequency; FEV₁, forced expiratory volume in 1 second.