Increase in failed swallows from pre- to post-lung transplant esophageal function testing is associated with acute rejection

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

	Total (N = 55)	Decreased failed swallows post-transplant (n = 16)	Unchanged failed swallows post-transplant (n = 17)	Increased failed swallows post-transplant (n = 22)	P value (χ2 or ANOVA)
Follow up, mean (years)	2.77 (SD 1.96)	2.98 (SD 1.56)	2.42 (SD 1.81)	2.89 (SD 2.35)	0.71
Male sex	36 (65.4)	12 (75.0)	13 (76.5)	11 (50.0)	0.14
BMI, mean	26.9 (SD 4.34)	25.7 (SD 3.15)	28.5 (SD 3.74)	26.4 (SD 5.21)	0.23
Age at transplant, mean	61.0 (SD 7.58)	61.3 (SD 7.92)	62.0 (SD 7.70)	60.1 (SD 7.47)	0.97
White race	49 (89.1)	16 (100)	16 (94.1)	17 (77.3)	0.06
Pulmonary diagnosis
ILD	42 (76.4)	13 (81.2)	12 (70.6)	17 (77.3)	0.76
IPF	28 (50.9)	9 (56.2)	8 (47.1)	11 (50.0)	0.86
COPD	11 (20.0)	3 (18.7)	4 (23.5)	4 (18.2)	0.91
Cardiac function, baseline
LVEF, mean	59.9 (SD 5.26)	58.8 (SD 4.74)	59.7 (SD 4.71)	60.9 (SD 6.03)	0.13
PaP, mean (mmHg)	26.6 (SD 10.1)	25.6 (SD 10.7)	28.4 (SD 12.7)	26.0 (SD 7.40)	0.47
PCWP, mean (mmHg)	10.1 (SD 4.71)	10.6 (SD 4.99)	10.3 (SD 4.98)	9.64 (SD 4.46)	0.59
PVR, mean (dynes∙sec∙cm-5)	244 (SD 189)	236 (SD 196)	283 (SD 257)	220 (SD 109)	0.76
Pulmonary function, baseline
FVC	2.25 (SD 0.91)	2.48 (SD 0.78)	2.29 (SD 1.10)	2.06 (SD 0.83)	0.44
FVC, %-pred	0.54 (SD 0.18)	0.60 (SD 0.18)	0.54 (SD 0.21)	0.50 (SD 0.14)	0.65
FEV1	1.68 (SD 0.81)	1.94 (SD 0.79)	1.67 (SD 0.96)	1.50 (SD 0.68)	0.38
FEV1, %-pred	0.52 (SD 0.22)	0.60 (SD 0.24)	0.50 (SD 0.27)	0.48 (SD 0.16)	0.85
FEV1/FVC	0.74 (SD 0.19)	0.76 (SD 0.16)	0.71 (SD 0.20)	0.74 (SD 0.20)	0.96
TLC, %-pred	0.62 (SD 0.29)	0.67 (SD 0.22)	0.58 (SD 0.21)	0.63 (SD 0.38)	0.26
Bilateral lung transplant	50 (90.9)	14 (87.5)	15 (88.2)	21 (95.4)	0.63
CMV mismatch	22 (40.0)	7 (43.7)	8 (47.1)	7 (31.8)	0.59
Increased risk donor	26 (47.3)	10 (62.5)	6 (35.3)	10 (45.4)	0.29
Pre-transplant AET, mean1 (%)	2.45 (SD 2.29)	2.64 (SD 2.80)	2.58 (SD 1.62)	2.27 (SD 2.36)	0.44
Post-transplant AET, mean2 (%)	2.41 (SD 5.28)	3.51 (SD 8.27)	3.26 (SD 4.54)	0.89 (SD 1.52)	0.33
Post-transplant infection	50 (90.9)	15 (93.7)	17 (100)	18 (81.8)	0.13
Post-transplant PPI	42 (76.4)	14 (87.5)	12 (70.6)	16 (72.7)	0.45
Pre-transplant failed swallows, mean	0.13 (SD 0.19)	0.27 (SD 0.20)	0	0.13 (SD 0.18)	< 0.0001
Post-transplant failed swallows, mean	0.17 (SD 0.23)	0.10 (SD 0.10)	0	0.34 (SD 0.27)	< 0.0001
Change in failed swallows, mean	+0.03 (SD 0.23)	-0.18 (SD 0.18)	0	+0.21 (SD 0.21)	< 0.0001

¹Available in 37/55 subjects.

²Available in 54/55 subjects.

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; AET: Acid Exposure Time; PPI: Proton pump inhibitor. Increased risk donors were those with hepatitis C infection. Post-transplant infection were those with infection detected on bronchoalveolar lavage prior to pulmonary decline.

Table 2 Cox multivariate analysis demonstrating the risk of acute rejection in patients with change in failed swallows as a continuous variable from pre- to post-lung transplant, controlling for confounders

Covariate	Cox multivariate analysis hazard ratios for ACR	P value
Change in failed swallows, per 10% increase	1.20 (1.01-1.43)	0.03
Borderline (AET 4%-6%) vs Normal (AET < 4%) pre-transplant acid reflux	0.32 (0.04-2.49)	0.27
Abnormal (AET > 6%) vs Normal (AET < 4%) pre-transplant acid reflux	1.33 (0.17-10.4)	0.79
Lungs transplanted	1.64 (0.20-13.6)	0.65
Age at transplant	0.99 (0.92-1.06)	0.70

ACR: Acute cellular rejection; AET: Acid exposure time.

Table 3 Cox multivariate analysis demonstrating the risk of acute rejection in patients with post-lung transplant hypocontractility, compared to post-transplant normal motility, controlling for confounders

Covariate	Cox multivariate analysis hazard ratios for ACR	P value
Post-transplant hypocontractility vs post-transplant normal motility	2.63 (1.11-11.8)	0.03
Post-transplant hypercontractility vs post-transplant normal motility	2.81 (0.80-9.85)	0.10
Borderline (AET 4%-6%) vs normal (AET < 4%) pre-transplant acid reflux	0.43 (0.05-3.35)	0.42
Abnormal (AET > 6%) vs normal (AET < 4%) pre-transplant acid reflux	1.65 (0.20-13.8)	0.64
Lungs transplanted	2.45 (0.30-20.2)	0.40
Age at transplant	0.99 (0.92-1.06)	0.77

ACR: Acute cellular rejection; AET: Acid exposure time.

Table 4 Correlation with change in failed swallows

	Spearman’s correlation	P value
Baseline FVC, %-predicted	R = -0.19	0.16
Baseline FEV1, %-predicted	R = -0.16	0.23
Baseline FEV1/FVC	R = -0.02	0.87
Baseline TLC, %-predicted	R = -0.32	0.05
Change in bolus clearance	R = -0.45	0.004
Change in ineffective swallows	R = +0.51	< 0.0001

FVC: Forced vital capacity; FEV1: Forced expiratory volume; TLC: Total lung capacity.