Tolerability and Feasibility of the Upper Esophageal Sphincter Assist Device in Preventing Acute and Chronic Allograft Rejection Among Lung Transplant Recipients.

GOALS: 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. BACKGROUND: 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. STUDY: 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. RESULTS: 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. CONCLUSIONS: 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.

Lung transplantation and extracorporeal photopheresis: The answer to bronchiolitis obliterans?

Bronchiolitis obliterans (BO) is a rare condition characterized by narrowing of small airways. Although it can be caused by variety of conditions, most cases occur after lung and bone marrow transplantation in the form of graft-versus-host-disease and chronic rejection, respectively. Extracorporeal photopheresis (ECP) has emerged as a promising treatment for the condition, especially for BO after lung transplantation. Available data suggest that around two-thirds of patients may demonstrate either slowing or cessation of disease progression after treatment with ECP. Recent researches also provide interesting insights into possible mechanism of action of ECP in BO.

Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.

BACKGROUND: Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients. OBJECTIVE: To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious. DESIGN: Randomized, clinical trial. Patients were randomly assigned by a central automated system to treatment or placebo. Patients and investigators were blinded to treatment status. (ClinicalTrials.gov registration number: NCT00227370) SETTING: Multicenter trial involving 11 U.S. lung transplant centers. PATIENTS: 136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis. INTERVENTION: 9 additional months of oral valganciclovir (n = 70) or placebo (n = 66). MEASUREMENTS: The primary end point was freedom from CMV disease (syndrome or tissue-invasive) on an intention-to-treat basis 300 days after randomization. Secondary end points were CMV disease severity, CMV infection, acute rejection, opportunistic infections, ganciclovir resistance, and safety. RESULTS: CMV disease occurred in 32% of the short-course group versus 4% of the extended-course group (P < 0.001). Significant reductions were observed with CMV infection (64% vs. 10%; P < 0.001) and disease severity (110 000 vs. 3200 copies/mL, P = 0.009) with extended treatment. Rates of acute rejection, opportunistic infections, adverse events, CMV UL97 ganciclovir-resistance mutations, and laboratory abnormalities were similar between groups. During the 6 months after study completion, a low incidence of CMV disease was observed in both groups. LIMITATION: Longer-term effects of extended prophylaxis were not assessed. CONCLUSION: In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation.

Morphologic changes in explanted lungs after prostacyclin therapy for pulmonary hypertension.

Prostacyclin (PGI2) causes vasodilation and inhibition of platelet aggregation in vivo. PGI2 is also postulated to affect pulmonary vascular remodeling, at least partly through anti-proliferative effect via PGI2 receptor (PGIR). However, the mechanism(s) of action by which (PGI2) exerts its therapeutic effect is still not clear despite clear clinical benefit seen in severe pulmonary hypertension (PH) patients. We performed a histopathologic and morphometric study on the explanted lung tissues from PGI2-treated patients prior to lung transplantation (n = 9), in an attempt to elucidate morphologic changes associated with PGI2 treatment. Explanted lungs from PH patients without PGI2 treatment were examined as the control (n = 11). We also studied the possible differences in PGIR expression between the treated and untreated groups by immunohistochemical method. Seven out of 9 treated patients showed moderate to severe bronchial and perivascular inflammation, as opposed to only 1 such case in the control group. Five out of 9 treated cases showed moderate to severe alveolar edema with or without evidence of old hemorrhage, in contrast to only 1 case showing moderate alveolar edema in control patients. Morphometry did not reveal any significant difference between the two groups either in the % thickness of intima, media, or adventitia or in the density of plexiform lesions. Immunostain also failed to demonstrate any notable difference in PGIR expression. In conclusion, PGI2-treated cases revealed more pronounced pulmonary alveolar edema and inflammation, but no morphological evidence of altered vascular remodeling or PGIR expression after PGI2 therapy.

Donor transfer of pulmonary coccidioidomycosis in lung transplantation.

Transplant recipients living in endemic areas are at high risk of aerosol-transmitted fungal infections because of environmental exposure while on immunosuppressive drugs, as well as reactivation of latent infection from either the patient's or the donor's organs. The latter may account for early development of coccidioidomycosis after transplantation. We describe a case of pulmonary coccidioidomycosis in a lung transplant recipient who acquired the infection from the donor lung and presented with fulminant pneumonia in the immediate postoperative period.

Comparison of impedance cardiography to direct Fick and thermodilution cardiac output determination in pulmonary arterial hypertension.

Cardiac output (CO) is an important diagnostic and prognostic tool for patients with ventricular dysfunction. Pulmonary hypertension patients undergo invasive right heart catheterization to determine pulmonary vascular and cardiac hemodynamics. Thermodilution (TD) and direct Fick method are the most common methods of CO determination but are costly and may be associated with complications. The latest generation of impedance cardiography (ICG) provides noninvasive estimation of CO and is now validated. The purpose of this study was to compare ICG measurement of CO to TD and direct Fick in pulmonary hypertension patients. Thirty-nine enrolled patients were analyzed: 44% were male and average age was 50.8+/-17.4 years. Results for bias and precision of cardiac index were as follows: ICG vs. Fick (-0.13 L/min/m2 and 0.46 L/min/m2), TD vs. Fick (0.10 L/min/m2 and 0.41 L/min/m2), ICG vs. TD (respectively, with a 95% level of agreement between -0.72 and 0.92 L/min/m2; CO correlation of ICG vs. Fick, TD vs. Fick, and ICG vs. TD was 0.84, 0.89, and 0.80, respectively). ICG provides an accurate, useful, and cost-effective method for determining CO in pulmonary hypertension patients, and is a potential tool for following responses to therapeutic interventions.

Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder following lung transplantation is more commonly of host origin.

CONTEXT: Posttransplantation lymphoproliferative disorder (PTLD) in patients who have undergone solid organ transplantation is thought to be mostly of host (ie, transplant recipient) origin, as opposed to being predominantly of donor origin, which is observed in patients who have undergone bone marrow transplantation. Donor-origin PTLDs reportedly follow a more indolent course than host-origin PTLDs. OBJECTIVE: To determine the origin of PTLD and its clinical implications in patients who have undergone lung transplantation. DESIGN: Patients' medical records were reviewed for clinical data. We performed a molecular study to determine the origin of abnormal lymphoid cells in 4 PTLD cases identified from our autopsy files. Each case underwent restriction fragment length polymorphism analysis using polymerase chain reaction-based genotyping for CYP2D6. Epstein-Barr virus (latent membrane protein 1) immunostaining and polymerase chain reaction analysis were performed on PTLD-involved tissues. RESULTS: Three of 4 PTLD cases were of host origin, and the remaining case was of donor origin. Epstein-Barr virus was detected by immunohistochemical and polymerase chain reaction methods in all PTLD-involved tissues that were examined. There was no apparent difference in clinical manifestations between host-origin and donor-origin PTLD cases in our study. CONCLUSIONS: The PTLDs in our patients who had undergone lung transplantation were Epstein-Barr virus-positive and mostly of host origin, without any notable clinical difference from donor-origin PTLD.