Respiratory Impedance is Associated with Ventilation and Diffusing Capacity in Patients with Idiopathic Pulmonary Fibrosis Combined with Emphysema

Figures & data

Table 1 Baseline Characteristics (n = 47)

Parameter	IPF (n = 29)	CPFE (n = 18)	P-value
Age, y	72 (66–76)	75 (70–79)	0.224
Sex, male/female, n	19/10	17/1	0.033
BMI, kg m^−2	22.0 (20.5–23.4)	23.2 (21.9–25.5)	0.057
Smokers, n (%)	21 (75.0)	16 (100.0)	0.037
Smoking, pack-years	28 (1–39)	58 (45–81)	<0.001
mMRC dyspnea scale, 0/1/2/3/4, n	11/10/5/1/2	6/7/2/1/2	0.943
LDH, U/L	232 (204–254)	219 (183–243)	0.216
KL-6, U/mL	727 (517–1005)	724 (480–1503)	0.905
Diagnosis, n (%)
HRCT, n (%)	20 (69.0)	14 (77.8)	0.739
HRCT and SLB, n (%)	9 (31.0)	4 (22.2)
Treatment
Nintedanib, n (%)	1 (3.4)	1 (5.6)	>0.999
Pirfenidone, n (%)	6 (20.7)	1 (5.6)	0.225
Prednisolone, n (%)	3 (10.3)	1 (5.6)	>0.999
LAMA, n (%)	1 (3.4)	2 (11.1)	0.549
LABA, n (%)	2 (6.9)	0 (0.0)	0.517

Notes: Data are median (interquartile range) and n (%), unless otherwise stated.

Abbreviations: BMI, body mass index; CPFE, combined pulmonary fibrosis and emphysema; HRCT, high-resolution computed tomography; IPF, idiopathic pulmonary fibrosis; KL-6, Krebs von den Lugen-6; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonist; LDH, lactate dehydrogenase; mMRC, modified Medical Research Council; SLB, surgical lung biopsy.

Figure 1 Inclusion flowchart.

Abbreviations: CPFE, combined pulmonary fibrosis with emphysema; IPF, idiopathic pulmonary fibrosis.

Table 2 Pulmonary Function Tests in Patients with and without Emphysema (n = 47)

Parameter	IPF (n = 29)	CPFE (n = 18)	P-value
VC, L	2.27 (1.81–3.02)	2.75 (2.43–3.21)	0.131
FVC, L	2.21 (1.63–2.88)	2.68 (2.33–3.08)	0.078
FVC % predicted, %	72.8 (63.2–83.4)	81.7 (63.7–94.4)	0.244
FEV1, L	2.07 (1.43–2.51)	2.17 (1.77–2.42)	0.444
FEV1% predicted, %	82.6 (67.5–92.4)	83.0 (65.8–89.9)	0.835
FEV1/FVC, %	87.8 (83.9–92.2)	81.9 (73.1–88.6)	0.019
FRC, L	2.21 (1.63–2.81)	2.53 (2.09–3.22)	0.175
RV, L	1.45 (1.11–1.85)	1.65 (1.02–2.06)	0.298
CC, L	1.24 (1.13–1.79)	1.64 (1.40–2.00)	0.126
CV, L	0.31 (0.21–0.56)	0.56 (0.34–1.13)	0.017
CV/VC, %	17.4 (11.4–21.1)	21.2 (18.5–29.6)	0.009
CV/VC % predicted, %	70.6 (43.2–87.8)	80.4 (66.1–111.8)	0.086
DLCO,mL/min/mmHg	9.30 (7.93–19.74)	8.06 (6.52–10.37)	0.358
DLCO% predicted, %	60.9 (55.7–78.4)	47.1 (41.0–72.2)	0.074
DLCO/VA, mL/min/mmHg/L	3.36 (2.51–3.73)	2.29 (2.12–2.64)	0.009
DLCO/VA % predicted, %	60.9 (55.7–78.4)	47.1 (41.0–72.2)	0.074

Note: Data are median (interquartile range).

Abbreviations: CC, closing capacity; CPFE, combined pulmonary fibrosis and emphysema; CV, closing volume; D_LCO, diffusing capacity for carbon monoxide; FEV₁, forced expiration volume in 1 s; FRC, functional residual capacity; FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; RV, residual volume; V_A, alveolar volume; VC, vital capacity.

Table 3 Oscillometry in Patients with and without Emphysema (n = 47)

Parameter	IPF (n = 29)	CPFE (n = 18)	P-value
R5, cmH2O/L/s
Expiratory	3.08 (2.63–4.28)	2.80 (2.38–3.26)	0.128
Inspiratory	2.53 (2.06–3.12)	2.40 (2.03–2.78)	0.477
Average	2.80 (2.31–3.90)	2.63 (2.20–3.18)	0.299
R20, cmH2O/L/s
Expiratory	2.43 (1.90–3.27)	2.14 (1.86–2.44)	0.168
Inspiratory	1.97 (1.52–2.62)	1.84 (1.57–2.14)	0.352
Average	2.19 (1.73–2.92)	1.97 (1.73–2.37)	0.246
R5-R20, cmH2O/L/s
Expiratory	0.81 (0.53–1.02)	0.76 (0.49–0.93)	0.511
Inspiratory	0.50 (0.24–0.69)	0.55 (0.31–0.71)	0.827
Average	0.65 (0.40–0.90)	0.65 (0.49–0.77)	0.718
X5, cmH2O/L/s
Expiratory	−0.76 (−1.05–-0.57)	−0.61 (−0.95–-0.46)	0.375
Inspiratory	−0.92 (−1.40–-0.68)	−0.72 (−0.96–-0.55)	0.050
Average	−0.95 (−1.23–-0.63)	−0.70 (−0.91–-0.59)	0.143
Δ	−0.28 (−0.41–-0.08)	−0.13 (−0.42–0.11)	0.370
Fres, Hz
Expiratory	10.53 (8.81–12.65)	9.33 (8.11–12.90)	0.657
Inspiratory	11.67 (9.44–12.67)	10.08 (9.37–11.96)	0.336
Average	10.95 (9.15–13.11)	10.17 (9.10–12.03)	0.519
Δ	1.18 (0.12–1.85)	1.40 (−1.26–2.20)	0.641
AX, cmH2O/L/s × Hz
Expiratory	3.14 (2.01–5.46)	2.43 (1.56–4.78)	0.416
Inspiratory	4.61 (2.54–6.83)	3.00 (2.10–4.44)	0.078
Average	4.23 (2.41–6.43)	3.04 (2.20–4.52)	0.251
Δ	1.12 (0.22–-2.59)	0.57 (−1.01–2.61)	0.491

Note: Data are median (interquartile range).

Abbreviations: AX, low-frequency reactance area; CPFE, combined pulmonary fibrosis and emphysema; Δ, a within-breath change in each parameter; Fres, resonant frequency; IPF, idiopathic pulmonary fibrosis; R5 and R20, respiratory resistance at 5 and 20 Hz, respectively; X5, respiratory reactance at 5 Hz.

Figure 2 Correlations between FVC and inspiratory X5 in patients with CPFE and IPF (n=18 and n=29, respectively). FVC % predicted was positively associated with inspiratory X5 in both the subgroups.

Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; r_S, Spearman’s rank correlation coefficient; X5, respiratory reactance at 5 Hz.

Figure 3 Correlations between inspiratory X5 and diffusing capacity in patients with CPFE and IPF (n=18 and n=29, respectively). (A) A scatter plot between inspiratory X5 and D_LCO % predicted. (B) A scatter plot between inspiratory X5 and D_LCO/V_A percent predicted. Inspiratory X5 was positively associated with both D_LCO % predicted and D_LCO/V_A % predicted only in patients with CPFE.

Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; D_LCO, diffusing capacity for carbon monoxide; IPF, idiopathic pulmonary fibrosis; r_S, Spearman’s rank correlation coefficient; V_A, alveolar volume; X5, respiratory reactance at 5 Hz.

Figure 4 Correlations between FVC and diffusing capacity in patients with CPFE and IPF (n=18 and n=29, respectively). (A) A scatter plot between FVC % predicted and D_LCO % predicted. (B) A scatter plot between FVC % predicted and D_LCO/V_A % predicted. D_LCO % predicted and D_LCO/V_A % predicted were positively associated with FVC % predicted only in patients with CPFE.

Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; D_LCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; r_S, Spearman’s rank correlation coefficient; V_A, alveolar volume.

Figure 5 Correlations between CV/VC, FVC, and expiratory X5 in patients with CPFE and IPF (n=18 and n=29, respectively). (A) A scatter plot between CV/VC and FVC % predicted. (B) A scatter plot between CV/VC and expiratory X5. CV/VC correlated with expiratory X5 and FVC % predicted only in patients with IPF.

Abbreviations: CPFE, combined pulmonary fibrosis and emphysema; CV/VC, closing volume/vital capacity; FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; r_S, Spearman’s rank correlation coefficient; X5, respiratory reactance at 5 Hz.