Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury

Table 1 Baseline characteristics demonstrating homogeneity of the pulmonary transplant study population

	Total	Normal distal reflux exposure	Increased distal reflux exposure
	(n = 32)	(n = 13)	(n = 19)
Follow-up (yr), median	1.3
Male sex	15 (46.9)	7 (53.8)	8 (42.1)
BMI, mean ± SD	26.7 ± 4.97	26.7 ± 4.47	26.7 ± 5.40
Age at transplant (yr), mean	54.7 ± 10.8	57.6 ± 9.01	52.7 ± 11.7
White race	30 (93.7)	13 (100)	17 (89.5)
Pulmonary diagnosis
IPF	15 (46.9)	3 (23.1)	12 (63.2)
COPD	6 (18.7)	3 (23.1)	3 (15.8)
CF	6 (18.7)	2 (15.4)	4 (21.0)
COP	2 (6.25)	2 (15.4)	0
AAT	1 (3.13)	1 (7.69)	0
Sarcoid	1 (3.13)	1 (7.69)	0
Other	1 (3.13)	1 (7.69)	0
Cardiac function, Baseline
LVH
None	27 (84.4)	11 (84.6)	16 (84.2)
Any	5 (15.6)	2 (15.4)	3 (15.8)
LVEF, mean ± SD	0.59 ± 0.05	0.58 ± 0.06	0.60 ± 0.05
PCWP, mean ± SD	9.97 ± 4.62	11.5 ± 4.99	8.89 ± 4.15
PVR1, mean ± SD	224.4 ± 89.0	243.3 ± 100.1	210.0 ± 79.6
Pulmonary function, Baseline
FVC	1.91 ± 0.71	2.00 ± 0.84	1.85 ± 0.63
FVC, %-pred	0.48 ± 0.14	0.50 ± 0.16	0.47 ± 0.12
FEV1	1.22 ± 0.60	1.07 ± 0.67	1.32 ± 0.54
FEV1, %-pred	0.39 ± 0.18	0.33 ± 0.17	0.43 ± 0.17
FEV1/FVC	0.65 ± 0.24	0.54 ± 0.24	0.73 ± 0.21
Lungs transplanted
Unilateral	15 (46.9)	7 (53.8)	8 (42.1)
Bilateral	17 (53.1)	6 (46.1)	11 (57.9)
Post-transplant PPI	24 (75.0)	10 (76.9)	14 (73.7)
Deaths, all cause	8 (25.0)	2 (15.4)	6 (31.6)
Deaths, pulmonary-related	7 (21.9)	2 (15.4)	5 (26.3)
Early allograft injury	16 (50.0)	5 (38.5)	11 (57.9)
BOS	2 (6.25)	1 (7.69)	1 (5.26)

¹PVR was not measured in two subjects. BMI: Body mass index; IPF: Idiopathic pulmonary fibrosis; COPD: Chronic obstructive pulmonary disease; CF: Cystic fibrosis; COP: Cryptogenic organizing pneumonia; AAT: Alpha-1-antitrypsin deficiency; LVH: Left ventricular hypertrophy; LVEF: Left ventricular ejection fraction; PCWP: Pulmonary capillary wedge pressure; PVR: Pulmonary vascular resistance; FVC: Forced vital capacity; %-pred: Percent of predicted value; FEV1: Forced expiratory volume in 1 second; PPI: Proton pump inhibitor; BOS: Bronchiolitis obliterans syndrome.

Table 2 Comparison of Cox univariate analyses of pH parameters of acid reflux and corresponding impedance measures of total reflux

	Univariate hazard ratio for time to acute rejection (95%CI)	P value
pH parameter of acid reflux
Acid reflux exposure, upright	1.01 (0.93-1.09)	0.87
Acid reflux exposure, recumbent	1.06 (0.92-1.21)	0.42
Acid reflux exposure, overall	1.03 (0.93-1.15)	0.52
Elevated acid reflux exposure (> 4.2%)	1.06 (0.92-1.21)	0.93
Total acid reflux episodes	1.00 (0.97-1.03)	0.90
Acid clearance	1.00 (1.00-1.00)	0.13
Impedance parameter of total reflux
Total reflux exposure, upright	1.11 (0.98-1.25)	0.11
Total reflux exposure, recumbent	1.25 (1.04-1.50)	0.011
Total reflux exposure, overall	1.18 (1.01-1.36)	0.031
Elevated total reflux exposure (> 1.4%)	1.88 (0.65-5.42)	0.24
Total reflux episodes	1.01 (1.00-1.02)	0.20
Bolus clearance	1.09 (1.01-1.17)	0.021

¹Statistically significant results in impedance measures of total bolus reflux.

Table 3 Area under the receiver operating characteristic curve or c-statistic comparing prediction value of pH-testing and corresponding impedance measures of reflux for early allograft injury

	Area under ROC/Harrell’s c-stat
pH parameter of reflux
Acid reflux exposure, upright	0.58
Acid reflux exposure, recumbent	0.69
Acid reflux exposure, overall	0.61
Elevated acid reflux exposure (> 4.2%)	0.39
Total acid reflux episodes	0.60
Acid clearance	0.64
Impedance parameter of reflux
Total reflux exposure, upright	0.63
Total reflux exposure, recumbent	0.74
Total reflux exposure, overall	0.67
Elevated total reflux exposure (> 1.4%)	0.77
Total reflux episodes	0.64
Bolus clearance	0.74

Note that all values deriving from impedance measures are greater than those from pH measures, suggesting that impedance data are better predictors.