One major consequence of lung transplantation is the development of oropharyngeal dysphagia. This systematic review aims to appraise and synthesize the available evidence of the use of instrumental assessments to outline the characteristics of post-lung transplant dysphagia.

Following the identification of appropriate search terms for the question, a literature search was conducted in PubMed, Scopus, and the Health and Medical Collection of Proquest Research Library and included records between inception and September 14, 2023. Search strategies included the use of text words and subject headings (e.g., MeSH and Index terms) related to (1) dysphagia or swallowing (swallow*, deglutition disorder*), (2) lung transplant (lung transplant*, post-operative, post-lung), and (3) complications (adverse effects, *complications, treatment outcome).

The literature search strategy yielded a total of 883 studies from the electronic database search, with no additional records identified through other sources. After the removal of duplicates (n = 96), a total of 787 studies were screened through title and abstracts which eliminated 775 studies. Six studies were ultimately included in the systematic review. The selected articles included patients who underwent lung transplantation and all but one study utilized a retrospective design. A lack of transparency regarding instrumental evaluation protocols (videofluoroscopic [VFSS] and Flexible Endoscopic Evaluation of Swallowing [FEES]) including the number and bolus types used during the instrumental evaluations appeared as a theme in the studies included. The Penetration-Aspiration Scale (PAS) was systematically utilized to measure dysphagia safety outcome. Handling of the PAS scale was not consistent across studies, however penetration or aspiration ranged from 52.4% up to 100%. Additionally, silent aspiration rates ranged from 14.2% to 61.9%.

This review sought to describe the post-operative swallowing function and its physiological parameters following lung transplantation. We examined the results reported and the methods utilized in obtaining these results in the existing literature. Limited reporting practices for physiological parameters were found, however the airway invasion was reported in all studies with variation in degrees of swallowing safety related deficits, with PAS being the most widely used scale to describe airway invasion depth and response. Future studies exploring dysphagia outcomes post-lung transplant should comment on the altered physiological mechanisms of the swallow to further expand on the physiological deficits observed following transplantation in this group and allow for treatment planning.

Level 1.

We surveyed esophageal motility laboratories affiliated with adult pulmonary transplant centers to determine esophageal function testing (EFT) practices.

Gastroesophageal reflux and esophageal dysmotility are associated with worse lung transplant outcomes, yet no consensus guidelines for EFT exist in this population.

A deidentified online survey was sent to gastrointestinal motility laboratory directors of 49 academic and community-affiliated medical centers that perform lung transplants. Practice characteristics, including annual lung transplant volume and institutional EFT practices pre-lung transplantation and post-lung transplantation were queried. Respondents were categorized by transplant volume into small and large programs based on median annual volume.

Among 35 respondents (71% response rate), the median annual transplant volume was 37, and there were 18 large programs. Institutional EFT protocols were used pretransplant by 24 programs (68.6%) and post-transplant by 12 programs (34.2%). Among small and large programs, 52.9% and 72.2% always obtained high-resolution manometry before transplant, respectively. Endoscopy before transplant was performed more often in small programs (n=17, 100%) compared with large programs (n=15,83.3%). Pretransplant endoscopy ( P =0.04), barium esophagram ( P <0.01), and high-resolution manometry ( P =0.04) were more common than post-transplant. In contrast, post-transplant reflux monitoring off-therapy was more common than pretransplant ( P =0.01). In general, pulmonologists direct referrals for EFT and gastroenterology consultation (n=28, 80.0%), with symptoms primarily prompting testing.

In the absence of established guidelines, substantial variability exists in pretransplant and post-transplant EFT, directed by pulmonologists. Standardized EFT protocols and gastroenterologist-directed management of esophageal dysfunction has potential to improve lung transplant outcomes.

Gastrointestinal (GI) complications in lung transplant recipients can occur any time during the post-operative period, leading to prolonged morbidity and mortality. Despite the negative association between GI complications and patient outcomes, little is known about their incidence and risk factors for their development in pediatric lung transplant recipients.

We performed a retrospective chart review at one pediatric tertiary center to describe the frequency of GI complications in lung transplant recipients. We identified potential risk factors for the diagnosis of gastroparesis, gastroesophageal reflux disease (GERD) and aspiration in the post-transplant period. Lastly, we investigated the association of these complications with mortality and graft survival.

84.3% of lung transplant recipients experienced at least one GI complication in the post-transplant period. Gastroparesis (52.9%), GERD (41.2%), and oropharyngeal dysphagia/laryngeal penetration (33.3%) were the most common complications diagnosed. Post-operative opioid exposure was a risk factor for gastroparesis, with the odds increasing 3.0% each day a patient was prescribed opioids (p = .021). The risk of death or retransplant in individuals who experienced gastroparesis was 2.7 times higher than those not diagnosed with gastroparesis (p = .027).

Exposure to opioids in the post-operative period is a risk factor for gastroparesis and a prolonged hospitalization placed patients at risk for aspiration. Gastroparesis was associated with increased patient mortality and graft failure, while aspiration and GERD had no effect on long term outcomes. Future prospective studies investigating the relationship between opioid use and the development of a gastroparesis are necessary to improve patient outcomes.

Fundoplication is known to improve allograft outcomes in lung transplant recipients by reducing retrograde aspiration secondary to gastroesophageal reflux disease, a modifiable risk factor for chronic allograft dysfunction. Laparoscopic Nissen fundoplication has historically been the anti-reflux procedure of choice, but the procedure is associated with discernable rates of postoperative dysphagia and gas-bloat syndrome. Laparoscopic Toupet fundoplication, an alternate anti-reflux surgery with lower rates of foregut complications in the general population, is the procedure of choice on our institution's lung transplant protocol. In this work, we evaluated the efficacy and safety of laparoscopic Toupet fundoplication in our lung transplant recipients.

A prospective case series of 44 lung transplant recipients who underwent laparoscopic Toupet fundoplication by a single surgeon between September 2018 and November 2020 was performed. Preoperative and postoperative results from 24-h pH, esophageal manometry, gastric emptying, and pulmonary function studies were collected alongside severity of gastroesophageal reflux disease and other gastrointestinal symptoms.

Median DeMeester score decreased from 25.9 to 5.4 after fundoplication (p < 0.0001), while percentage of time pH < 4 decreased from 7 to 1.1% (p < 0.0001). The severity of heartburn and regurgitation were also reduced (p < 0.0001 and p = 0.0029 respectively). Overall, pulmonary function, esophageal motility, gastric emptying, severity of bloating, and dysphagia were not significantly different post-fundoplication than pre-fundoplication. Patients with decreasing rates of FEV1 pre-fundoplication saw improvement in their rate of change of FEV1 post-fundoplication (p = 0.011). Median follow-up was 32.2 months post-fundoplication.

Laparoscopic Toupet fundoplication provides objective pathologic acid reflux control and symptomatic gastroesophageal reflux improvement in lung transplant recipients while preserving lung function and foregut motility. Thus, laparoscopic Toupet fundoplication is a safe and effective antireflux surgery alternative in lung transplant recipients.

We define mixed esophageal disease (MED) as a disorder of esophageal structure and/or function that produces variable signs or symptoms, simulating-fully or in part other well-defined esophageal conditions, such as gastroesophageal reflux disease, esophageal motility disorders, or even neoplasia. The central premise of the MED concept is that of an overlap syndrome that incorporates selected clinical, endoscopic, imaging, and functional features that alter the patient's quality of life and affect natural history, prognosis, and management. In this article, we highlight MED scenarios frequently encountered in medico-surgical practices worldwide, posing new diagnostic and therapeutic challenges. These, in turn, emphasize the need for better understanding and management, aiming towards improved outcomes and prognosis. Since MED has variable and sometimes time-evolving clinical phenotypes, it deserves proper recognition, definition, and collaborative, multidisciplinary approach, be it pharmacologic, endoscopic, or surgical, to optimize therapeutic outcomes, while minimizing iatrogenic complications. In this regard, it is best to define MED early in the process, preferably by teams of clinicians with expertise in managing esophageal diseases. MED is complex enough that is increasingly becoming the subject of virtual, multi-disciplinary, multi-institutional meetings.

Gastroesophageal reflux disease (GERD) is common in patients who have undergone lung transplantation and is associated with poorer outcomes, but guidelines are lacking to direct management strategies in this population. We assessed the diagnostic yield of impedance metrics compared to pH-metry alone for detecting GERD among lung transplant recipients and evaluated their association with clinical outcomes. We performed a retrospective cohort study of consecutive patients who underwent lung transplantation. Demographic data, acid exposure time (AET), number of reflux episodes, mean nocturnal baseline impedance (MNBI), post-reflux swallowing-induced peristaltic wave index (PSPWI), and clinical outcomes including mortality were collected. The relationship between GERD metrics and clinical outcomes was assessed using Wilcoxon signed-rank test and Fisher's exact test as appropriate. Of the 76 patients studied, 29 (38%) had GERD based on abnormal AET after lung transplantation. One (1.3%) patient had GERD based on elevated number of reflux episodes and abnormal distal MNBI detected GERD in 19 (26%) patients, resulting in 62% sensitivity and 94% specificity. Two (2.6%) patients had normal PSPWI. Patients with low distal MNBI had significantly decreased forced expiratory volume in 1 second (FEV1) at 3-year posttransplant compared to those without low distal MNBI (P = 0.03). Three-year survival was significantly worse among patients with elevated AET (66.7% vs. 89.1%, P = 0.03) but not with low distal MNBI (68.4% vs. 84.3%, P = 0.18). Abnormal AET is more sensitive for detecting GERD than other reflux metrics studied and is associated with survival, suggesting pH-metry alone may be sufficient to guide GERD management after lung transplant.

We aimed to evaluate a novel upper esophageal sphincter (UES) assist device loaner program for the prevention of acute cellular rejection and chronic lung allograft dysfunction among lung transplant (LTx) recipients.

Laryngopharyngeal reflux can lead to chronic microaspiration and LTx rejection. The UES assist device applies external pressure at the level of UES to decrease reflux.

We prospectively enrolled and issued UES assist devices to consecutive transplant patients referred for gastrointestinal motility testing from 2016 to 2020. Device tolerability was defined by successful utilization as a bridge to ambulatory pH monitoring and/or antireflux procedure, or as permanent therapy. Incidence of rejection was analyzed before, during, and after device implementation.

Twenty-six participants were issued devices (15 pathologic, 5 physiological, 6 unknown reflux status), none of whom developed acute rejection episodes or chronic lung allograft dysfunction while using the device. Thirteen adopted the device promptly after transplantation (mean 1.7 mo) and remained free of rejection episodes over a mean 24.7 months of follow-up. Among those with pathologic reflux, lag time to device adoption strongly correlated with the development of rejection ( r =0.8, P =0.0006). There was no such correlation among those with physiological reflux. Five developed acute rejection after device return.

The device was tolerated by a majority of LTx patients and appears feasible as a barrier measure in the prevention of rejection. Delayed treatment of laryngopharyngeal reflux may lead to early allograft failure; therefore, the UES assist device should be given important consideration in transplant protection.

The number of lung transplantations is progressively increasing worldwide, providing new challenges to interprofessional teams and the intensive care units. The outcome of lung transplantation recipients is critically affected by a complex interplay of particular pathophysiologic conditions and risk factors, knowledge of which is fundamental to appropriately manage these patients during the early postoperative course. As high-grade evidence-based guidelines are not available, the authors aimed to provide an updated review of the postoperative management of lung transplantation recipients in the intensive care unit, which addresses six main areas: (1) management of mechanical ventilation, (2) fluid and hemodynamic management, (3) immunosuppressive therapies, (4) prevention and management of neurologic complications, (5) antimicrobial therapy, and (6) management of nutritional support and abdominal complications. The integrated care provided by a dedicated multidisciplinary team is key to optimize the complex postoperative management of lung transplantation recipients in the intensive care unit.

Esophageal pathology has been identified as a bad prognostic factor in lung transplantation (LTx). This study aims to assess the esophageal disorders present post-LTx, under treatment with proton pump inhibitors, and their putative impact on the graft.

Prospective, observational study of LTx patients. Digestive factors were assessed by manometry and pH-metry at 6 months post-LTx and under proton pump inhibitor treatment. We assessed the association between esophageal disorders and graft function and acute rejection (AR) and chronic lung allograft dysfunction (CLAD).

Out of 76 post-LTx patients, 27% showed gastroesophageal reflux disease (GERD), 55% showed inadequate gastric inhibition, and 59% showed esophageal motility disorders (EMDs). We observed a greater incidence of AR from 3 months post-LTx in the presence of EMD (P ≤ .05). No significant differences were observed in GERD or EMD prevalence or in survival between patients with or without CLAD. The maximum forced expiratory volume in 1 second (FEV1) achieved after bilateral LTx was significantly (P = .022) lower in patients with EMD vs without EMD.

At 6 months post-LTx, there is a high percentage of esophageal disorders (GERD and EMDs). No esophageal disorder is associated with CLAD or with survival, although EMDs are associated with a greater incidence of AR and lower graft function.

Lung transplantation is a high-risk, but lifesaving, procedure for patients with end-stage lung disease. Although 1-year survival is high, long-term survival is not nearly as high, due mainly to acute and chronic rejection. Bronchiolitis obliterans syndrome is the most common type of chronic rejection and often leads to poor outcomes. For this reason, esophageal testing in the lung transplant population has become a major issue, and this article discusses the evidence behind esophageal testing, the importance of esophageal dysmotility gastroesophageal reflux disease, both acidic and nonacidic reflux, and aspiration and the treatment of these findings.

Gastroesophageal reflux (GER) in recipients of lung transplant (LTX) is associated with chronic allograft rejection, presumably via microaspiration that damages airway epithelium. Most LTX programs perform a single post-LTX esophageal study to evaluate for GER; the efficacy of this test is unclear.

Patients with 1 year of post-LTX follow-up, including routine bronchoscopies with bronchoalveolar lavage fluid (BALF) samples as well as high-resolution esophageal manometry and pH probe monitoring (HREMpH), were evaluated. BALF samples were analyzed with competitive enzyme-linked immunosorbent assay to detect bile salts, which are indicative of aspiration. These results were compared to results of HREMpH studies post LTX.

Ninety BALF samples were analyzed for bile salts and acted as disease positive for this evaluation. Of the 13 HREMpH cases, 8 were positive for GER, but only 3 were positive for bile salts via assay. Of the 5 HREMpH-negative cases, 2 experienced aspiration. A solitary HREMpH study had 60.0% sensitivity and 37.5% specificity with positive and negative likelihood ratios: 0.96 and 1.07, respectively.

Microaspiration appears to be an intermittent phenomenon, and HREMpH screening poorly correlates with BALF evidence of aspiration; which may not be adequate. As aspiration detection is crucial in this population, further analysis is warranted.

Gastroesophageal reflux and esophageal dysmotility are common in patients with advanced lung disease and are associated with allograft dysfunction after lung transplantation. The effect of transplantation on reflux and esophageal motility is unclear. The aim of this study was to describe the changes in esophageal function occurring after lung transplantation. A retrospective cohort study was performed on lung transplant candidates evaluated at a tertiary care center between 2015 and 2016. A total of 76 patients who underwent lung transplantation had high-resolution manometry and ambulatory pH-metry before and after transplant. Demographic data, esophageal function testing results, and clinical outcomes such as pulmonary function testing were collected and analyzed using appropriate statistical tests and multivariable regression. Of the 76 patients, 59 (78%) received a bilateral transplant. There was a significant increase in esophageal contractility posttransplant, with an increase in median distal contractile integral from 1470 to 2549 mmHg cm s (P < 0.01). There were 19 patients with Jackhammer esophagus posttransplant, including 15 patients with normal motility pretransplant. Nine patients with ineffective or fragmented peristalsis pretransplant had normal manometry posttransplant. Abnormal pH-metry was observed in 35 (46%) patients pretransplant and 29 (38%) patients posttransplant (P = 0.33). Patients with gastroesophageal reflux disease posttransplant had less improvement in pulmonary function at one year, as measured by forced expiratory volume (P = 0.04). These results demonstrate that esophageal contractility increases significantly after lung transplantation, with an associated change in motility classification. In comparison, gastroesophageal reflux does not worsen, but is associated with worse pulmonary function, posttransplant.

lung transplantation (LTx) is a viable option for most patients with end-stage lung diseases. Esophageal motor disorders (EMD) are frequent in candidates for LTx, but there is very little data about changes in esophageal motility post-LTx.

the aim of our study was to assess esophageal motor disorders by high resolution manometry (HRM) both pre-LTx and six months post-LTx in patients with and without organ rejection.

HRM (Manoscan®) was performed in 57 patients both pre-LTx and six months post-LTx. HRM plots were analyzed according to the Chicago classification 3.0.

EMD were found in 33.3% and in 49.1% of patients pre-LTx and post-LTx, respectively, and abnormal peristalsis was more frequently found post-LTx (p = 0.018). Hypercontractile esophagus was frequently found post-LTx (1.8% and 19.3% pre-LTx and post-LTx, respectively). Esophagogastric junction (EGJ) morphology changed significantly pre-LTx and post-LTx; type I (normal) was more frequent post-LTx (63-2% and 82.5% respectively, p = 0.007). EMD were more frequent post-LTx in both the non-rejection and rejection group, although particularly in the rejection group (43.2% and 69.2% respectively, p = 0.09). EMD such as distal spasm, hypercontractile esophagus and EGJ outflow obstruction were also observed more frequently post-LTx in the rejection group.

significant changes in esophageal motility were observed pre-LTx and particularly post-LTx; hypercontractile esophagus was a frequent EMD found post-LTx. EMD were more frequent in the group of patients that experienced organ rejection compared to the non-rejection group. EMD leading to an impaired esophageal clearance should be considered as an additional factor that contributes to LTx failure.

Aspiration is a syndrome with variable respiratory manifestations that span acute, life-threatening illnesses, such as acute respiratory distress syndrome, to chronic, sometimes insidious, respiratory disorders such as aspiration bronchiolitis. Diagnostic testing is limited by the insensitivity of histologic testing, and although gastric biomarkers for aspiration are increasingly available, none have been clinically validated. The leading mechanism for microaspiration is thought to be gastroesophageal reflux disease, largely driven by the increased prevalence of gastroesophageal reflux across a variety of respiratory disorders, including chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, and chronic cough. Failure of therapies targeting gastric acidity in clinical trials, in addition to increasing concerns about both the overuse of and adverse events associated with proton pump inhibitors, raise questions about the precise mechanism and causal link between gastroesophageal reflux and respiratory disease. Our review summarizes key aspiration syndromes with a focus on reflux-mediated aspiration and highlights the need for additional mechanistic studies to find more effective therapies for aspiration syndromes.

Lung transplants belong in the group of organ transplants with poorer outcomes, with acute rejection and bronchiolitis obliterans being cited as major causes of this. Poor allograft evolution has been associated with multiple factors, including those related to esophagogastric disease. In patients with end-stage pulmonary conditions eligible for a lung transplant gastroesophageal reflux (GER), esophageal dysmotily, and gastroparesis are highly prevalent and worsen upon transplantation, which may compromise transplant viability. High-resolution impedance manometry and long-term impedance pH-metry studies provide a new perspective where reflux and dysmotility share the limelight with changes in the diagnostic approach and in potential therapies.

Gastroesophageal reflux disease and esophageal dysmotility are prevalent in patients with advanced lung disease and are associated with graft dysfunction following lung transplantation. As a result, many transplant centers perform esophageal function testing as part of the wait-listing process but guidelines for testing in this population are lacking. The aim of this study is to describe whether symptoms of gastroesophageal reflux correlate with abnormal results on pH-metry and high-resolution manometry and can be used to identify those who require testing. We performed a retrospective cohort study of 226 lung transplant candidates referred for high-resolution manometry and pH-metry over a 12-month period in 2015. Demographic data, results of a standard symptom questionnaire and details of esophageal function testing were obtained. Associations between the presence of symptoms and test results were analyzed using Fisher's exact tests and multivariable logistic regression. The most common lung disease diagnosis was interstitial lung disease (N = 131, 58%). Abnormal pH-metry was seen in 116 (51%) patients and the presence of symptoms was significantly associated with an abnormal study (p < 0.01). Dysmotility was found in 98 (43%) patients, with major peristaltic or esophageal outflow disorders in 45 (20%) patients. Symptoms were not correlated with findings on esophageal high-resolution manometry. Fifteen of 25 (60%) asymptomatic patients had an abnormal manometry or pH-metry. These results demonstrate that in patients with advanced lung disease, symptoms of gastroesophageal reflux increase the likelihood of elevated acid exposure on pH-metry but were not associated with dysmotility. Given the proportion of asymptomatic patients with abnormal studies and associated post-transplant risks, a practice of universal high-resolution manometry and pH-metry testing in this population is justifiable.

Chronic aspiration of small volumes of oral and gastric contents can lead to lung disease. This process is less familiar than the acute aspiration syndromes, which can create confusion in terminology as well as with radiologic and pathologic definitions.

In this study we analyze a series of cases of patients with chronic occult aspiration to better define the disease process.

Twenty-five patients with chronic occult aspiration as defined pathologically on lung biopsy were studied by means of retrospective review of their case records. Clinical associations and radiologic and pathologic patterns were noted.

Among patients with chronic occult aspiration, there was a high prevalence of gastroesophageal reflux disease (96%), esophageal dysfunction (40%), oropharyngeal/laryngeal dysfunction (40%), hiatal hernias (32%), obstructive sleep apnea (32%), and obesity (52%). The radiologic presentation was typically one of multilobar centrilobular nodularity, tree-in-bud, and airway thickening, with a subset of patients having evidence of fibrosis. The disease presented pathologically with exogenous lipoid pneumonia, poorly formed granulomas, and foreign body-type multinucleated giant cells with or without foreign material. Pathologic fibrosis was also seen.

In this study, chronic occult aspiration was associated with a number of comorbid conditions and a spectrum of radiologic and pathologic patterns, which in some patients included fibrosis.

Respiratory function deteriorates over time after lung transplant. Reflux disease with pulmonary complications is a possible cause of this decline. This case series we aim to assess whether respiratory function improves after Nissen fundoplication in lung transplant patients and if surgery reduces gastroesophageal reflux disease (GERD) symptoms and use of proton pump inhibitors (PPIs).

A retrospective case series of lung transplant patients with reflux disease and Nissen fundoplication. Clinical symptoms, pH-metry data, use of PPIs were recorded before the procedure and up to 18 months postoperatively. The FEV1 values before and after Nissen fundoplication were recorded at 3 monthly intervals. Patients' satisfaction scores were recorded before operation and postoperatively.

A total of 64 lung transplant patients were selected. After Nissen fundoplication, the pH studies were done on 26 patients. The mean overall acid exposure fraction was 1.03% (P<0.05). FEV1 declined for 6 months postoperatively and then gradually improved. The comparison of FEV1 at 3 months preoperatively to 3 months postoperatively showed no significant difference (P=0.067) as well as at 6 months. A significant improvement in clinical GERD symptoms was achieved after antireflux surgery; however, the patients remained receiving PPIs.

NF has been established as a safe operation for lung transplant patients. Late Nissen fundoplication did not improve lung function significantly amongst lung transplanted patients; however, patients with symptomatic GERD may have benefited from Nissen fundoplication in terms of symptom relief. A multicenter randomized control trial is needed to assess the effect of early unselected reflux control on respiratory function and graft survival.

Acid reflux has been associated with poorer outcomes after lung transplantation. Standard pre-transplant reflux assessment has not been universally adopted. Non-acid reflux may also induce a pulmonary inflammatory cascade, leading to acute and chronic rejection. Esophageal multichannel intraluminal impedance and pH testing (MII-pH) may be valuable in standard pre-transplant evaluation. We assessed the association between pre-transplant MII-pH measures and early allograft injury in lung transplant patients.

This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant MII-pH at a tertiary center from 2007 to 2012. Results from pre-transplant MII-pH, cardiopulmonary function testing, and results of biopsy specimen analysis of the transplanted lung were recorded. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods to assess the associations between MII-pH measures and development of acute rejection or lymphocytic bronchiolitis.

Thirty patients (46.7% men; age, 54.2 years) met the inclusion criteria. Pre-transplant cardiopulmonary function and pulmonary diagnoses were similar between outcome groups. Prolonged bolus clearance (hazard ratio [HR], 4.11; 95% confidence interval [CI], 1.34-12.57; p = 0.01), increased total distal reflux episodes (HR, 4.80; 95% CI, 1.33-17.25; p = 0.02), and increased total proximal reflux episodes (HR, 4.43; 95% CI, 1.14-17.31; p = 0.03) were significantly associated with decreased time to early allograft injury. Kaplan-Meier curves also demonstrated differences in time to rejection by prolonged bolus clearance (p = 0.01) and increased total distal reflux episodes (p = 0.01). Sub-group analysis including only patients with MII-pH performed off proton pump inhibitors (n = 24) showed similar results.

Prolonged bolus clearance, increased total distal reflux episodes, and increased total proximal reflux episodes on pre-transplant MII-pH were associated with decreased time to early allograft injury after lung transplantation. Routine pre-transplant MII-pH may provide clinically relevant data regarding transplant outcomes and peri-transplant care.

The aim of this review is to give an overview of the clinical circumstances presenting before lung transplant that may have negative repercussions on the long and short-term prognosis of the transplant. Methods for screening and diagnosis of common comorbidities with negative impact on the prognosis of the transplant are proposed, both for pulmonary and extrapulmonary diseases, and measures aimed at correcting these factors are discussed. Coordination and information exchange between referral centers and transplant centers would allow these comorbidities to be detected and corrected, with the aim of minimizing the risks and improving the life expectancy of transplant receivers.

Advanced pulmonary disorders are linked to esophageal hypomotility and reflux disease. However, characterization of esophageal function using high resolution manometry (HRM) and ambulatory pH monitoring, segregation by pulmonary pathology, and comparison to traditional reflux disease are all limited in the literature.

Over a 4 year period, 73 patients (55.2 ± 1.3 years, 44F) were identified who underwent esophageal function testing as part of lung transplant evaluation for advanced pulmonary disease (interstitial lung disease, ILD = 47, obstructive lung disease, OLD = 24, other = 2). Proportions of patients with motor dysfunction (≥ 80% failed sequences = severe hypomotility) and/or abnormal reflux parameters (acid exposure time, AET ≥ 4%) were determined, and compared to a cohort of 1081 patients (48.4 ± 0.4 years, 613F) referred for esophageal function testing prior to antireflux surgery (ARS).

The proportion of esophageal body hypomotility was significantly higher within advanced pulmonary disease categories (35.6%), particularly ILD (44.7%), compared to ARS patients (12.1%, P < 0.0001). Abnormal AET was noted in 56.5%, and was similar between ILD and OLD, but less frequent than in the ARS group (P = 0.04). Post-transplant chronic rejection trended towards association with pretransplant elevated AET in OLD (P = 0.08) but not ILD. Mortality was not predicted by esophageal motor pattern or reflux evidence.

Interstitial lung disease has a highly significant association with esophageal body hypomotility. Consequently, prevalence of abnormal esophageal acid exposure is high, but implications for post lung transplant chronic rejection remain unclear.

Bronchiolitis obliterans syndrome (BOS) is a condition of progressive airflow obstruction that affects a majority of lung transplant recipients and limits long-term posttransplant survival. Although epithelial injury appears central to the development of BOS, little is known regarding the specific epithelial cell types that are affected in this condition. We hypothesized that BOS would involve preferential injury to the secretory Clara cells that function in innate defense and epithelial repair. To test this hypothesis, we assessed tissue transcript, tissue protein and lung fluid protein expression of Clara cell secretory protein (CCSP), a marker for Clara cells, in lung transplant recipients with BOS, BOS-free patients and in donor controls. Our results demonstrate that CCSP tissue transcript and protein expression are significantly reduced in lung transplant recipients with BOS compared to BOS-free or donor controls. In addition, we demonstrate that CCSP protein levels are significantly reduced in the lung fluid of patients with BOS compared to BOS-free controls, in cross-sectional and longitudinal analysis. Collectively, these complementary results illustrate that BOS involves a selective alteration in the distribution and function of bronchiolar Clara cells.