J.P. Gagermeier

Gastroesophageal reflux disease after lung transplantation: pathophysiology and implications for treatment.

BACKGROUND Gastroesophageal reflux disease (GERD) is thought to be a risk factor for the development or progression of chronic rejection after lung transplantation. However, the prevalence of GERD and its risk factors, including esophageal dysmotility, hiatal hernia and delayed gastric emptying after lung transplantation, are still unknown. In addition, the prevalence of Barretts esophagus, a known complication of GERD, has not been determined in these patients. The purpose of this study was to determine the prevalence and extent of GERD, as well as the frequency of these risk factors and complications of GERD in lung transplant patients. METHODS Thirty-five consecutive patients underwent a combination of esophageal function testing, upper endoscopy, barium swallow, and gastric emptying scan after lung transplantation. RESULTS In this patient population, the prevalence of GERD was 51% and 22% in those who had been retransplanted. Of patients with GERD,36% had ineffective esophageal motility (IEM), compared with 6% of patients without GERD (P = .037). No patient demonstrated hiatal hernia on barium swallow. The prevalence of delayed gastric emptying was 36%. The prevalence of biopsy-confirmed Barretts esophagus was 12%. CONCLUSION Our study shows that, after lung transplantation, more than half of patients had GERD, and that GERD was more common after retransplantation. IEM and delayed gastric emptying are frequent in patients with GERD. Hiatal hernia is rare. The prevalence of Barretts esophagus is not negligible. We conclude that GERD is highly prevalent after lung transplantation, and that delayed gastric emptying and Barretts esophagus should always be suspected after lung transplantation because they are common risks factors and complications of GERD.

Laparoscopic Antireflux Surgery for Gastroesophageal Reflux Disease After Lung Transplantation

BACKGROUND Although gastroesophageal reflux disease (GERD) is highly prevalent in lung transplantation, the pathophysiology of GERD in these patients is unknown. We hypothesize that the pathophysiology of GERD after lung transplantation differs from that of a control population, and that the 30-d morbidity and mortality of laparoscopic antireflux surgery (LARS) are equivalent in both populations. METHODS We retrospectively compared the pathophysiology of GERD and the 30-d morbidity and mortality of 29 consecutive lung transplant patients with 23 consecutive patients without lung transplantation (control group), all of whom had LARS for GERD between November 2008 and May 2010. RESULTS Both groups had a similar prevalence of endoscopic esophagitis and Barretts esophagus , comparable manometric profiles, and similar prevalence of abnormal peristalsis. However, hiatal hernia was more common in controls than in lung transplant patients (57% versus 24%; P = 0.04). Lung transplant patients had a higher prevalence and severity of proximal GERD (65% versus 33%; P = 0.04). The 30-d morbidity and mortality following LARS were similar in both groups regardless of the higher surgical risk of lung transplants (median ASA class: 3 versus 2 for controls, P < 0.001). CONCLUSIONS These results show that despite similar manometric profiles, lung transplant patients are more prone to proximal reflux than the general population with GERD; the prevalence of endoscopic esophagitis and Barretts esophagus is the same in both groups of patients; a hiatal hernia is uncommon after lung transplantation; and the morbidity and mortality of LARS are the same for lung transplant patients as the general population with GERD.

Pulmonary immune changes early after laparoscopic antireflux surgery in lung transplant patients with gastroesophageal reflux disease

BACKGROUND The biologic mechanisms by which laparoscopic antireflux surgery (LARS) might influence the inflammatory process leading to bronchiolitis obliterans syndrome are unknown. We hypothesized that LARS alters the pulmonary immune profile in lung transplant patients with gastroesophageal reflux disease. METHODS In 8 lung transplant patients with gastroesophageal reflux disease, we quantified and compared the pulmonary leukocyte differential and the concentration of inflammatory mediators in the bronchoalveolar lavage fluid (BALF) 4 weeks before LARS, 4 weeks after LARS, and 12 months after lung transplantation. Freedom from bronchiolitis obliterans syndrome (graded 1-3 according to the International Society of Heart and Lung Transplantation guidelines), forced expiratory volume in 1 second trends, and survival were also examined. RESULTS At 4 weeks after LARS, the percentages of neutrophils and lymphocytes in the BALF were reduced (from 6.6% to 2.8%, P = 0.049, and from 10.4% to 2.4%, P = 0.163, respectively). The percentage of macrophages increased (from 74.8% to 94.6%, P = 0.077). Finally, the BALF concentration of myeloperoxide and interleukin-1β tended to decrease (from 2109 to 1033 U/mg, P = 0.063, and from 4.1 to 0 pg/mg protein, P = 0.031, respectively), and the concentrations of interleukin-13 and interferon-γ tended to increase (from 7.6 to 30.4 pg/mg protein, P = 0.078 and from 0 to 159.5 pg/mg protein, P = 0.031, respectively). These trends were typically similar at 12 months after transplantation. At a mean follow-up of 19.7 months, the survival rate was 75% and the freedom from bronchiolitis obliterans syndrome was 75%. Overall, the forced expiratory volume in 1 second remained stable during the first year after transplantation. CONCLUSIONS Our preliminary study has demonstrated that LARS can restore the physiologic balance of pulmonary leukocyte populations and that the BALF concentration of pro-inflammatory mediators is altered early after LARS. These results suggest that LARS could modulate the pulmonary inflammatory milieu in lung transplant patients with gastroesophageal reflux disease.

A review of the potential applications and controversies of non‐invasive testing for biomarkers of aspiration in the lung transplant population

Davis CS, Gagermeier J, Dilling D, Alex C, Lowery E, Kovacs EJ, Love RB, Fisichella PM. A review of the potential applications and controversies of non‐invasive testing for biomarkers of aspiration in the lung transplant population.
Clin Transplant 2010: 24: E54–E61.

The Prevalence and Extent of Gastroesophageal Reflux Disease Correlates to the Type of Lung Transplantation

Background: Evidence is increasingly convincing that lung transplantation is a risk factor of gastroesophageal reflux disease (GERD). However, it is still not known if the type of lung transplant (unilateral, bilateral, or retransplant) plays a role in the pathogenesis of GERD. Study Design: The records of 61 lung transplant patients who underwent esophageal function tests between September 2008 and May 2010, were retrospectively reviewed. These patients were divided into 3 groups based on the type of lung transplant they received: unilateral (n=25); bilateral (n=30), and retransplant (n=6). Among these groups we compared: (1) the demographic characteristics (eg, sex, age, race, and body mass index); (2) the presence of Barrett esophagus, delayed gastric emptying, and hiatal hernia; and (3) the esophageal manometric and pH-metric profile. Results: Distal and proximal reflux were more prevalent in patients with bilateral transplant or retransplant and less prevalent in patients after unilateral transplant, regardless of the cause of their lung disease. The prevalence of hiatal hernia, Barrett esophagus, and the manometric profile were similar in all groups of patients. Conclusions: Although our data show a discrepancy in prevalence of GERD in patients with different types of lung transplantation, we cannot determine the exact cause for these findings from this study. We speculate that the extent of dissection during the transplant places the patients at risk for GERD. On the basis of the results of this study, a higher level of suspicion of GERD should be held in patients after bilateral or retransplantation.

Usefulness of pH monitoring in predicting the survival status of patients with scleroderma awaiting lung transplantation

BACKGROUND Patients with scleroderma and end-stage lung disease (ESLD) have a very high prevalence of gastroesophageal reflux disease (GERD). Because GERD has been associated with aspiration in those with ESLD, and because those with scleroderma are particularly prone to develop severe GERD, there is some concern that GERD may contribute to shorten survival in patients with scleroderma awaiting lung transplantation. Therefore, we hypothesized that esophageal pH monitoring could predict survival of those with scleroderma and ESLD awaiting lung transplantation and that the severity of reflux can impact survival. METHODS We conducted a retrospective analysis of all scleroderma patients referred for lung transplantation who underwent esophageal manometry and pH monitoring since August 2008. We identified 10 patients in whom we calculated and compared the area under the curve for each receiver operating characteristic curve of the following variables: DeMeester score, forced expiratory volume in 1 s (FEV1), %predicted FEV1, forced vital capacity (FVC), %predicted FVC, diffusion capacity for carbon monoxide (DLco), and %predicted DLco. RESULTS The DeMeester score nominally outperformed FEV1, FVC, and DLco. Receiver operating characteristic curve analysis was also used to define the optimal DeMeester score (65.2) in differentiating survival status, as determined by maximizing sensitivity and specificity. Based on this value, we calculated the 1-y survival from the time of the esophageal function testing, which was 100% in seven patients with a DeMeester score of <65.2, and 33% in three patients with a score >65.2 (P = 0.01). The latter patients had greater total time pH < 4, greater time pH < 4 in the supine position, greater total episodes of reflux, and higher prevalence of absent peristalsis. The single survivor with a DeMeester score >70 had also proximal reflux, underwent antireflux surgery, and is alive 1201 d after transplant. CONCLUSIONS Our study shows that esophageal pH monitoring can predict survival status in patients with scleroderma awaiting lung transplantation and that the severity of reflux can impact the 1-y survival rate. Therefore, esophageal pH monitoring should be considered early in patients with scleroderma and ESLD, as this test could appropriately identify those in whom laparoscopic antireflux surgery should be performed quicker to prevent GERD and its detrimental effects in patients awaiting lung transplantation.

Subtherapeutic ganciclovir (GCV) levels and GCV‐resistant cytomegalovirus in lung transplant recipients

Cytomegalovirus (CMV) infection results in significant morbidity and mortality in lung transplant recipients. Ganciclovir (GCV) has dramatically reduced complications caused by CMV infections. Unfortunately, GCV resistance is identified in 5–10% of CMV‐infected patients. Mismatched CMV status and ongoing replication due to immunosuppression are risk factors for drug resistance. Whether subtherapeutic GCV levels contribute to resistance remains unknown.

Challenges in the diagnosis of 2009 H1N1 in a lung transplant patient and the long-term implications for prevention and treatment: a case report.

Although respiratory viral infections have been associated with acute rejection and bronchiolitis obliterans syndrome, the long-term impact of the novel pandemic influenza A (2009 H1N1) virus on lung transplant patients has not been defined. We describe the diagnostic challenges and long-term consequences of 2009 H1N1 infection in a lung transplant patient, discuss the potential implications for prevention and treatment, and conclude that even timely antiviral therapy may be insufficient to prevent long-term morbidity.