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

Abstract

BACKGROUND

The pathophysiology behind gastroesophageal reflux disease and its association with poor outcomes after lung transplantation is incompletely understood. The physiologic impact of lung transplantation on pulmonary function, intrathoracic pressures, and vagal innervation may affect esophageal motility, bolus clearance and reflux risk. However, the effect of changes in esophageal function after lung transplantation on the risk of poor post-transplant outcomes remains unclear.

AIM

To evaluate the association between change in esophageal motility pre-/post-lung transplantation and rejection outcome.

METHODS

This was a retrospective cohort study of lung transplant recipients who underwent both pre-and post-transplant esophageal testing including high resolution manometry (HRM) at a tertiary center. Acute cellular rejection (ACR) was defined histologically per International Society for Heart and Lung Transplantation criteria. Univariate analyses were performed using student’s t-test, χ² test, and Spearman’s correlation where appropriate. Multivariable time-to-event analysis using Cox proportional hazards model was applied. Subjects not meeting ACR outcome were censored at death or date of last clinic visit.

RESULTS

55 subjects (65% men, mean age: 61, median follow-up: 840 days) were included, with 17 (31%) experiencing ACR. Increase in failed swallows correlated with lower baseline total lung capacity (TLC) (R = -0.32, P = 0.05) and decreased post-transplant esophageal bolus clearance (R = -0.45, P = 0.004). On multivariable analysis, post-transplant hypomotility independently predicted increased ACR (HR: 3.62, 95%CI: 1.11-11.8; P = 0.03). Kaplan-Meier analysis demonstrated increased ACR for subjects with increased vs unchanged failed swallows post-transplant (P = 0.048). On Cox regression, a 20% elevated risk of ACR was found for every 10% increase in failed swallows, after controlling for confounders including reflux severity

CONCLUSION

Esophageal hypomotility, specifically an increase in failed swallows on HRM, from pre- to post-lung transplantation was independently associated with ACR. Additionally, lower baseline TLC correlated with increase in failed swallows, suggesting restrictive lung disease may be associated with post-transplant esophageal hypomotility. Lung transplantation may affect esophageal function and contribute to rejection outcomes. Routine esophageal function testing may help identify patients at higher risk for poor lung transplantation outcomes.

Key Words: Esophageal dysmotility; High-resolution manometry; Ineffective esophageal motility; Failed swallows; Lung transplantation; Acute rejection

Core Tip: Gastroesophageal reflux has been associated with poor outcomes after lung transplantation, though the pathophysiology remains unclear. Lung transplantation itself may modulate this risk through impacts on pulmonary function and intrathoracic pressures, which alters esophageal motility to affect bolus clearance and reflux severity. Our study demonstrated that increased failed swallows from pre- to post-transplant testing was associated with increased risk of acute rejection after lung transplant, and was inversely correlated with baseline percent-predicted total lung capacity. The physiologic impact of lung transplantation may therefore affect esophageal function and contribute to rejection outcomes, suggesting a need for routine manometric testing in this high-risk patient population.

INTRODUCTION

Gastroesophageal reflux disease (GERD) is a known potent risk factor for poor outcomes after lung transplantation. It is specifically associated with the development of acute cellular rejection (ACR), bronchiolitis obliterans syndrome and chronic lung allograft dysfunction[1,2]. Bronchoalveolar lavage studies of transplanted patients with GERD show increased bile acids and inflammatory proteins compared to patients without GERD, suggesting that mechanistically, microaspiration from GERD may lead to inflammation in the transplanted lung resulting in decreased function[3].

Ineffective esophageal motility has a well-established link to GERD and is also independently associated with acute lung transplant rejection[4]. This may have resulted from a similar mechanism of impaired esophageal clearance leading to microaspiration of esophageal content/refluxate and lung inflammation. The relationship between esophageal motility and lung transplantation appears to be bidirectional, as lung transplantation has been shown to affect motility and reflux in myriad ways. A 2019 study by Masuda et al[5] of 112 lung transplant patients in a single tertiary care center found that half had changes in manometric diagnosis after transplant, with most showing improved peristalsis. In the same study, lung transplantation was associated with increased prevalence of delayed gastric emptying, which was posited to be caused by operative vagus nerve injury. The vagus nerve also innervates the esophagus, so additional impacts on esophageal function may be expected. The relationship between lung transplant and esophageal function remains an area of active research, and can be challenging due to the lack of consistent esophageal testing standards in the peri-transplant setting across institutions[6].

To better understand this issue, the present study aims to investigate the relationship between change in esophageal contractile function before vs after lung transplant, and pulmonary physiology, other measures of esophageal function, and lung transplant outcomes. We hypothesize that patients with an increase in failed swallows after lung transplant will have increased risk of ACR following lung transplantation.

MATERIALS AND METHODS

Study design

This was a retrospective cohort study of lung transplant recipients older than 18 years at a tertiary care center who underwent HRM both pre- and post-transplantation between 2015-2022. The study was approved by the Mass General Brigham Healthcare Institutional Review Board.

Inclusion and exclusion criteria

Participants included adults who underwent single or bilateral lung transplantation. Only patients undergoing initial primary lung transplant were included. Patients with incomplete HRM data, no available follow-up histologic assessment for ACR, and pre-transplant antireflux surgery were excluded.

Data collection

Demographic, clinical, and transplant-specific data were collected from electronic health records for subjects meeting inclusion and exclusion criteria. Demographic data included sex, body mass index (BMI), age at transplantation, and race. Clinical data included pulmonary diagnosis, echocardiogram and right heart catheterization results, pulmonary function testing data, esophageal motility parameters based on HRM, CMV serostatus, number of lungs transplanted, donor risk profile, and post-transplant proton pump inhibitor (PPI) use. Pre- and post-transplant acid exposure time (AET) on multichannel intraluminal impedance-pH testing was used as a measure of baseline reflux severity. ABO compatibility was ensured for all donors and recipients prior to transplant. The primary outcome was ACR, defined histologically per International Society for Heart and Lung Transplantation (ISHLT) criteria based on routine post-transplant surveillance bronchoscopy biopsy results. Subjects not meeting the outcome were censored at death or last clinic visit. Secondary outcomes were post-transplant pulmonary infections and use of PPI.

Pre- and post-transplant HRM

Before transplantation, all patients underwent HRM using the Diversatek Healthcare system (Milwaukee, WI, United States). This system featured a solid-state catheter with 32 circumferential pressure sensors spaced 1 cm apart. The catheter was inserted transnasally, with its distal sensors positioned in the proximal stomach to ensure proper placement across the lower esophageal sphincter. After a brief adaptation period, patients completed ten 5-mL liquid swallows while in a supine position. The results were analyzed using BioView software (version 5.6.3.0; Diversatek Healthcare). Parameters of interest included overall manometric diagnosis; distal contractile integral in the calculation of failed swallows (< 100 mmHg∙sec∙cm³), weak swallows (100-450 mmHg∙sec∙cm³), and ineffective swallows (total failed + weak swallows); and bolus clearance (complete clearance of bolus on impedance manometry, reported as swallows with complete bolus clearance divided by total number of swallows). A diagnosis of ineffective esophageal manometry (IEM) was made in accordance with current guidelines, with failed swallows ≥ 50%, or ineffective swallows ≥ 70%. HRM was repeated post-transplant at 3 months, or as soon as patient was clinically able to complete testing.

Post-transplant outcomes

After transplantation, patients received a standard immunosuppressive regimen consisting of azathioprine or mycophenolate, tacrolimus, and methylprednisolone. Additionally, 42 patients were prescribed PPI due to a history of GERD or newly developed heartburn symptoms. Bronchoscopy and biopsies for surveillance were conducted at 1-, 3-, 6-, and 12-months post-transplant as part of standard institutional protocol. If patients developed symptoms indicative of infection or rejection, additional bronchoscopies were performed. Acute rejection was classified using ISHLT criteria, with grade A1B0 rejection considered clinically significant if patients showed symptoms and received pulsed steroid therapy, or if repeated bronchoscopy revealed ongoing grade A rejection.

Statistical analysis

Continuous variables were summarized using means and standard deviations or medians and interquartile ranges as appropriate. Baseline characteristics were analyzed by applying the Student’s t-test for continuous variables and Fisher’s exact test for categorical variables. Spearman’s correlation assessed relationships between esophageal motility parameters and clinical variables. Cox proportional hazards models evaluated the association between changes in failed swallows and time-to-ACR, adjusting for confounders such as baseline GERD severity and lung disease etiology. Kaplan-Meier curves stratified by changes in failed swallows were generated to visualize event-free survival. Statistical analyses were performed using SAS 9.3 software (SAS Institute Inc, Cary, NC, United States).

RESULTS

Cohort and outcome characteristics

Fifty-five patients met eligibility criteria for the study, including 36 (65%) men. Mean BMI and age at transplant were 26.9 (SD 4.34) kg/m² and 61 (SD 7.58) years, respectively. With regards to indications for lung transplant, 42 (76.4%) had interstitial lung disease (ILD) and 11 (20%) had chronic obstructive pulmonary disease. Idiopathic pulmonary fibrosis, a subset of ILD, accounted for 28 (50.9%) of the pulmonary diagnoses. The median post-transplant follow-up was 840 days.

Cardiopulmonary status was as expected in this lung transplant cohort. There was evidence of right sided cardiac dysfunction with mean pulmonary arterial pressure of 26.6 mmHg (SD 10.1), pulmonary capillary wedge pressure 10.1 mmHg (SD 4.71), and pulmonary vein resistance of 244 dynes/cm5 (SD 189). Pulmonary function was poor at time of lung transplantation, with forced vital capacity (FVC) 54% of predicted (SD 18%), forced expiratory volume in 1 second (FEV1) 52% of predicted (SD 22%), FEV1/FVC 74% (SD 19%), and total lung capacity (TLC) 62% of predicted (SD 29%). Nearly all patients (90.9%, n = 50) received bilateral lung transplant.

The above findings did not vary between subgroups with decreased, unchanged, or increased failed swallows after lung transplant (Table 1).

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.

With regards to the exposure variable of change in failed swallows following transplant, 16 patients had decreased failed swallows, 17 had unchanged failed swallows, and 22 had increased failed swallows post-transplant. The average change in failed swallows among those with decreased failed swallows was -18% and the average change in failed swallows among those with increased failed swallows was +21%, which represented a statistically significant difference across groups (P < 0.0001) (Table 1).

Regarding manometric diagnosis, esophagogastric junction dysfunction was observed in 1 patient pre-transplant and 3 patients post-transplant; hypocontractility (including findings of absent contractility and IEM) in 17 patients pre-transplant and 12 patients post-transplant; hypercontractility (including findings of distal esophageal spasm and jackhammer esophagus) in 5 pre-transplant and 9 post-transplant; and normal motility in 32 pre-transplant and 31 post-transplant. Overall, 10 subjects with normal motility pre-transplant developed a manometric disorder post-transplant, 9 subjects with a manometric disorder pre-transplant became normal post-transplant, 22 were normal pre- and post-transplant; and 13 had the same manometric diagnosis pre- and post-transplant. Only 1 patient had IEM pre-transplant and possible EGJOO post-transplant.

Predictors of ACR

Twenty patients (33%) experienced ACR during the follow-up period. In a multivariable Cox analysis of time to ACR, increased failed swallows by 10% was associated with increased risk of ACR (HR: 1.20, 95%CI: 1.01-1.43; P = 0.03), controlling for AET, number of lungs transplanted, and age (Table 2). Kaplan-Meier analysis confirmed the increased risk of ACR in subjects with increased failed swallows compared to those with no changes in failed swallows (Figure 1). Post-transplant hypocontractility was also associated with increased ACR risk compared to post-transplant normal motility (HR: 3.62, 95%CI: 1.11-11.8; P = 0.03) (Table 3). Of the 12 subjects with post-transplant hypocontractility, 9 had hypocontractility and 3 had normal motility prior to transplant, with a mean increase of 17% failed swallows.

Figure 1  Kaplan-Meier curve demonstrating increased risk of acute rejection with increased failed swallows compared to no change in failed swallows from pre- to post-lung transplant esophageal function.

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.

Correlations between motility and transit parameters

Changes in failed swallows were inversely correlated with baseline %-predicted TLC (R = -0.32, P = 0.05) and changes in bolus clearance (R = -0.45, P = 0.004), but directly correlated with changes in ineffective swallows (r = 0.51, P < 0.0001) (Table 4). No associations were noted with other demographic or cardiopulmonary data.

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.

DISCUSSION

GERD and esophageal motility disorders are common in individuals with advanced lung disease. There is growing awareness of how these esophageal abnormalities may contribute to the development and progression of various types of end-stage lung disease, as well as their impact on lung transplant outcomes. Given the poor standardization of peri-transplant esophageal testing[6], less research has focused on the impact of lung transplant surgery itself on esophageal motility and subsequent effects on transplant outcomes.

Our findings show that post-transplant esophageal hypocontractility is associated with increased ACR compared to normal motility. Specifically, higher proportion of failed swallows on HRM following lung transplant predicted ACR, with a significant effect size of 20% increased risk with each 10% rise in proportion of failed swallows. This is consistent with prior evidence that poor esophageal motility is associated with transplant rejection[4]. It also implies that any potential measures to preserve or improve esophageal function may help to optimize the long-term health of the lung allograft.

Some post-transplant factors that may affect esophageal function may be unavoidable, such as immunosuppression and anatomic changes to the thoracic cavity. Immunosuppressive medications, notably calcineurin inhibitors, are crucial for lung transplant success but may worsen esophageal function by causing de-differentiation of smooth muscle cells in molecular studies, which may have a negative impact on the smooth muscle of the thoracic esophagus to generate normal motility[7]. More specifically, the calcineurin inhibitor tacrolimus has been found to decrease calcium concentration in intestinal muscle and, in turn, decrease the tension generated by intestinal muscle tissue, leading to nausea, diarrhea, constipation, and pain[8]. Rare esophageal effects of tacrolimus have included esophageal ulceration, acute esophageal necrosis, and achalasia. Thoracoabdominal anatomy also inevitably changes after lung transplant. For example, in single lung transplant, the diaphragmatic crus thickens and increases the diaphragm height on the side of the transplant[9], resulting in asymmetric chest wall expansion and shift of the mediastinum towards the native lung during inspiration and towards the transplanted lung during exhalation[10]. These myriad changes to thoracic and mediastinal anatomy may encroach on the esophagus, affecting the Angle of His, which is known to influence reflux[11].

Other consequences of lung transplantation that may affect esophageal motility, such as phrenic nerve injury, could be potentially avoidable. Phrenic nerve injury is a known adverse outcome from lung transplant surgery, with incidence ranging from 9.3% to 43.3%, depending on how nerve injury was assessed[12,13]. This may influence reflux as the left phrenic nerve innervates the esophagogastric junction[14]. Thus, measures to reduce potential phrenic nerve injury may improve lung transplant outcomes. In fact, numerous evidence-based strategies have been developed to mitigate the risk of phrenic nerve injury during lung transplantation, including surgical techniques like bilateral anterior thoracotomy instead of clamshell incision, non-in situ transplantation, and intraoperative phrenic nerve monitoring[12,15,16].

We find expected associations between increased failed swallows and worsened esophageal bolus clearance, which may predispose to increased proximal migration of refluxate or reduced esophageal transit. Prior studies have similarly linked ineffective swallows with decreased esophageal clearance, increased proximal reflux, and worse lung function in patients with chronic lung diseases[17]. Patients with more severe hypomotility may, therefore, be at higher risk for poorer pulmonary and transplantation outcomes.

Prior literature is mixed regarding how restrictive vs obstructive lung disease relates to changes in esophageal function after transplant. A study of 62 patients who underwent HRM before and after lung transplant found that restrictive lung disease (RLD) patients were more likely than obstructive lung disease (OLD) patients to show esophageal motility improvement after transplant[18]. However, a different single-center study of 29 patients who received preoperative barium esophagram and post-operative HRM found the opposite - that patients with esophageal aperistalsis and OLD but not those with RLD had improved esophageal peristalsis after transplant[19]. Our study adds further data to this ongoing question. We found that baseline TLC was inversely correlated with change in failed swallows. This suggests that more severe restrictive pulmonary disease may be associated with higher risk of post-transplant esophageal hypomotility. One possible explanation for this finding is that in patients with RLD and smaller, fibrotic lungs, transplantation could lead to changes in thoracoabdominal anatomy that decreases esophageal contractility. Specifically, the introduction of larger more compliant lungs may shift the position of the esophagus or increase the esophageal pressure gradient, either of which could impact esophageal motility, particularly during the near-term recovery period. This hypothesis has some supporting evidence, as it is known that lung transplantation in RLD increases thoracic cavity volume, whereas in OLD the opposite occurs[20]. Another explanation could be that patients with RLD are more vulnerable to worsening esophageal motility than patients with OLD, especially given the underlying causes of some RLD such as connective tissue disorders and the higher prevalence of diaphragmatic dysfunction in this population, which may impact the crura and esophagogastric junction barrier function[21].

Our study has several strengths. First, we ensured consistency in pre- and post-transplant assessments by standardizing esophageal motility evaluation with HRM for all lung transplant candidates. To reduce ascertainment bias in detecting acute rejection, we followed a rigorous surveillance protocol, performing biopsies during bronchoscopy at 1, 3, 6, and 12 months, with additional diagnostic bronchoscopy triggered by clinical symptoms between those intervals. The baseline characteristics of our cohort aligned with previously reported data on rates of acute rejection, prevalence of esophageal dysmotility in pre-transplant evaluation, and indications for lung transplant. Our study also has several limitations. As a retrospective cohort study conducted at a single, high-volume academic institution specializing in lung transplantation, the demographic composition of the study population constrains the generalizability of results. Also, the small sample size of 55 patients decreases the power of our findings, although it is within the range of similar publications on this high-risk population, and may have contributed to non-significant trends observed in secondary outcomes. Future investigations with larger, more diverse samples may be necessary to validate these findings.

CONCLUSION

In conclusion, increased failed swallows from pre- to post-lung transplantation are associated with a higher risk of ACR. Baseline pulmonary physiology may influence these changes, highlighting the need for targeted post-transplant care strategies. Routine esophageal function testing including HRM alongside an enhanced understanding of the impact of esophageal dysmotility in lung transplant outcomes may guide future diagnostic and therapeutic interventions.