Increased reflux burden on pre-transplant reflux testing independently predicts significant pulmonary function decline after lung transplantation

Table 1 Baseline demographics and clinical characteristics of study cohort, n (%)

Characteristics	Total (n = 70)	Normal acid exposure (n = 52)	Increased acid exposure (n = 18)	P value
Follow up, (years), mean ± SD	2.23 ± 1.87	2.24 ± 2.03	2.22 ± 1.34	0.97
Male sex	41 (58.6)	30 (57.7)	11 (61.1)	1.00
BMI, mean ± SD	26.8 ± 4.56	27.4 ± 4.40	25.4 ± 4.80	0.11
Age at transplant, mean ± SD	56.3 ± 12.5	56.7 ± 12.5	55.0 ± 13.0	0.62
White race	67 (95.7)	51 (98.1)	16 (88.9)	0.16
Pulmonary diagnosis
ILD	40 (57.1)	28 (53.8)	12 (66.7)	0.41
IPF	22 (31.4)	14 (26.9)	8 (44.4)	0.24
COPD	15 (21.4)	13 (25.0)	2 (11.1)	0.32
Other	17 (24.3)	13 (25.0)	4 (22.2)	1.00
Cardiac function, baseline
LVEF, mean ± SD	60.9 ± 5.48	60.3 ± 5.72	62.7 ± 4.40	0.11
PaP, mean ± SD	26.6 ± 9.36	27.7 ± 10.3	23.5 ± 4.62	0.03
PCWP, (mm Hg), mean ± SD	10.3 ± 4.90	10.8 ± 5.18	8.82 ± 3.71	0.16
PVR (dynes/cm5), mean ± SD	225 ± 134	230 ± 145	212 ± 91.9	0.64
Pulmonary function, baseline
FVC, mean ± SD	2.00 ± 0.77	1.99 ± 0.67	2.03 ± 1.01	0.87
FVC, %-pred, mean ± SD	0.49 ± 0.15	0.50 ± 0.16	0.46 ± 0.12	0.29
FEV1, mean ± SD	1.36 ± 0.66	1.32 ± 0.59	1.47 ± 0.85	0.44
FEV1, %-pred, mean ± SD	0.42 ± 0.19	0.43 ± 0.20	0.40 ± 0.18	0.63
FEV1/FVC, mean ± SD	0.69 ± 0.23	0.68 ± 0.23	0.72 ± 0.22	0.62
Bilateral lung transplant	36 (51.4)	29 (55.8)	7 (38.9)	0.28
CMV mismatch	18 (25.7)	15 (28.8)	3 (16.7)	0.37
Increased risk donor	11 (15.7)	8 (15.4)	3 (16.7)	1.00
Post-transplant infection	30 (42.8)	23 (44.3)	7 (38.9)	0.79
Post-transplant PPI	54 (77.1)	38 (73.1)	16 (88.9)	0.21
≥ 20% FEV1 decline	18 (25.7)	11 (21.1)	7 (38.9)	0.21

Increased risk donors were those with hepatitis C infection. Post-transplant infection were those with infection detected on bronchoalveolar lavage prior to pulmonary decline.

BMI: Body mass index; IPF: Idiopathic pulmonary fibrosis; ILD: Interstitial lung fibrosis; COPD: Chronic obstructive pulmonary disease; CF: Cystic fibrosis; LVEF: Left ventricular ejection fraction; PaP: Pulmonary artery pressure; PCWP: Pulmonary capillary wedge pressure; PVR: Pulmonary vascular resistance; FVC: Forced vital capacity; %-pred: Percent predicted value; FEV1: Forced expiratory volume in 1 second; CMV: Cytomegalovirus; PPI: Proton pump inhibitor.

Table 2 Baseline demographics of cohort demonstrated no association with forced expiratory volume in 1 decline on time-to-event analysis

Characteristics	Univariate hazard ratio for pulmonary function decline (95%CI)	P value
Male sex	2.14 (0.67-6.87)	0.20
BMI	0.98 (0.87-1.09)	0.70
Age at transplant	1.00 (0.95-1.04)	0.85
White race	0.59 (0.08-4.59)	0.62
Pulmonary diagnosis
ILD	2.29 (0.71-7.39)	0.16
IPF	2.73 (0.94-7.89)	0.06
COPD	0	-
Other	0.91 (0.28-2.94)	0.87
Cardiac function, baseline
LVEF	0.19 (0-4512)	0.75
PaP (mm Hg)	1.00 (0.95-1.06)	0.85
PCWP (mm Hg)	1.00 (0.90-1.11)	0.98
PVR (dynes/cm5)	1.00 (0.99-1.00)	0.58
Pulmonary function, baseline
FVC	1.14 (0.62-2.11)	0.67
FVC, %-pred	0.30 (0.01-9.66)	0.49
FEV1	1.67 (0.84-3.32)	0.14
FEV1, %-pred	3.25 (0.24-43.9)	0.37
FEV1/FVC	6.21 (0.46-83.7)	0.17
Bilateral lung transplant	0.74 (0.25-2.16)	0.59
CMV mismatch	0.77 (0.21-2.76)	0.69
Increased risk donor	0.62 (0.08-4.84)	0.65
Post-transplant infection	1.40 (0.49-4.01)	0.53
Post-transplant PPI	1.57 (0.35-7.04)	0.55

Increased risk donors were those with hepatitis C infection. Post-transplant infection were those with infection detected on bronchoalveolar lavage prior to pulmonary decline.

CI: Confidence interval; BMI: Body mass index; IPF: Idiopathic pulmonary fibrosis; ILD: Interstitial lung fibrosis; COPD: Chronic obstructive pulmonary disease; CF: Cystic fibrosis; LVEF: Left ventricular ejection fraction; PaP: Pulmonary artery pressure; PCWP: Pulmonary capillary wedge pressure; PVR: Pulmonary vascular resistance; FVC: Forced vital capacity; %-pred: Percent predicted value; FEV1: Forced expiratory volume in 1 second; CMV: Cytomegalovirus; PPI: Proton pump inhibitor.

Table 3 Multichannel intraluminal impedance and pH measures and time to forced expiratory volume in 1 decline

Characteristics	Univariate hazard ratio for pulmonary function decline (95%CI)	P value	Multivariate analyses (separate models controlling for age, sex, BMI)	P value
Elevated AET (> 4.2%)	3.49 (1.15-10.6)	0.03	3.37 (1.08-10.6)	0.04
Elevated total reflux episodes (> 73)	1.09 (0.34-3.48)	0.89	1.45 (0.40-5.27)	0.57
Elevated proximal acid episodes (> 28)	3.34 (1.02-11.0)	0.04	3.29 (0.90-12.1)	0.07

CI: Confidence interval; BMI: Body mass index; AET: Acid exposure time.