Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux

Table 1 Baseline demographics between manometric diagnoses, mean ± SD

	Total (n = 181)	IEM (n = 31)	Normal motility (n = 130)	Other motility disorder (n = 20)
Follow-up (years)	2.43 ± 2.45	2.85 ± 2.77	2.43 ± 2.41	1.76 ± 2.11
Male sex	97 (53.6%)	20 (64.5%)	70 (53.8%)	7 (35.0%)
BMI	26.6 ± 4.37	25.8 ± 3.88	26.6 ± 4.55	28.0 ± 3.66
Age at transplant (years)	58.4 ± 10.2	57.9 ± 12.1	58.1 ± 10.2	61.6 ± 7.17
White race1	166 (92.2%)	24 (77.4%)	123 (94.6%)	20 (100%)
Pulmonary diagnosis
ILD	99 (54.7%)	19 (61.3%)	69 (53.1%)	11 (55.0%)
IPF	74 (40.9%)	14 (45.2%)	51 (39.2%)	9 (45.0%)
COPD	57 (31.5%)	7 (22.6%)	43 (33.1%)	7 (35.0%)
CF	17 (9.39%)	4 (12.9%)	13 (10.0%)	0 (0%)
Cardiac function2
LVEF (%)	61.7 ± 5.73	62.2 ± 5.79	61.4 ± 5.42	62.6 ± 7.55
PaP (mmHg)	27.7 ± 10.3	28.6 ± 11.0	27.3 ± 10.3	29.2 ± 8.91
PCWP (mmHg)	10.8 ± 4.96	9.06 ± 4.01	11.2 ± 5.15	11.5 ± 4.65
PVR (dynes/sec/cm-5)	252 ± 194	300 ± 238	233 ± 175	300 ± 217
Pulmonary function, baseline2
FVC	1.93 ± 0.82	1.97 ± 0.92	1.94 ± 0.81	1.77 ± 0.78
FVC, %-pred	50.1 ± 47.0	49.2 ± 18.4	50.1 ± 19.0	51.3 ± 24.4
FEV1	1.24 ± 0.68	1.39 ± 0.74	1.22 ± 0.68	1.15 ± 0.57
FEV1, %-pred	40.5 ± 20.4	44.1 ± 21.1	39.4 ± 20.1	42.6 ± 21.6
FEV1/FVC	0.66 ± 0.25	0.72 ± 0.22	0.64 ± 0.25	0.67 ± 0.26
Manometry results
Normal	130	0	130	0
IEM	31	31	0	0
DES	7	0	0	7
Jackhammer	7	0	0	7
EGJOO	6	0	0	6
Reflux monitoring
Acid reflux	69 (38.1%)	13 (41.9%)	50 (38.5%)	6 (30.0%)
Nonacid reflux2	42 (26.6%)	11 (39.3%)	30 (26.8%)	1 (5.56%)
Lungs transplanted
Unilateral	43 (23.8%)	6 (19.3%)	34 (26.1%)	3 (15.0%)
Bilateral	138 (76.2%)	25 (80.6%)	96 (73.8%)	17 (85.0%)
CMV mismatch	53 (29.3%)	7 (22.6%)	42 (32.3%)	4 (20.0%)
High-risk donor	69 (38.1%)	7 (22.6%)	52 (40.0%)	10 (50.0%)
Post-transplant PPI	128 (70.7%)	24 (77.4%)	92 (70.8%)	12 (60.0%)

¹Indicates statistically significant difference between ineffective esophageal motility and normal, P < 0.05.

²Indicates subjects with available data.

BMI: Body mass index; ILD: Interstitial lung disease; IPF: Idiopathic pulmonary fibrosis; COPD: Chronic obstructive pulmonary disease; CF: Cystic fibrosis; LVEF: Left ventricular ejection fraction; PaP: Pulmonary arterial pressure; PCWP: Pulmonary capillary wedge pressure; PVR: Pulmonary vascular resistance; FVC: Forced vital capacity; FEV1: Forces expiratory volume in 1 second; IEM: Ineffective esophageal motility; DES: Distal esophageal spasm; EGJOO: Esophagogastric junction outflow obstruction; CMV: Cytomegalovirus; PPI: Proton pump inhibitor.

Table 2 Cox univariate and multivariable analyses demonstrating the association between manometric diagnosis of ineffective esophageal motility as defined by CCv3.0 and acid reflux based on acid exposure time > 4.2%, and increased risk of acute rejection after lung transplantation

Covariate	Cox univariate analysis	P value	Cox multivariable analysis	P value
Ineffective esophageal motility	1.84 (1.03-3.30)	0.04	2.20 (1.18-4.11)	0.01
Nonacid reflux	2.16 (1.26-3.72)	0.005	2.10 (1.21-3.64)	0.009
Acid reflux	1.06 (0.63-1.76)	0.83	0.92 (0.53-1.61)	0.77
Body-mass Index	1.01 (0.95-1.06)	0.85	1.02 (0.96-1.09)	0.43
Age at transplant	1.00 (0.98-1.02)	0.94	1.00 (0.97-1.02)	0.93
Male gender	0.85 (0.51-1.41)	0.53	0.75 (0.44-1.29)	0.30