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Background: The number of cystic fibrosis (CF) patients undergoing lung transplantation continues to grow, as does the prevalence of multidrug-resistant (MDR) gram-negative rods. However, the posttransplant survival of patients with MDR pathogens, specifically pan-resistant Achromobacter xylosoxidans and Stenotrophomonas maltophilia, is poorly characterized., Methods: This was a retrospective review of CF patients (n = 186; all age, > 16 years) transplanted at the University of North Carolina from 1990 through 2013. Respiratory cultures before transplantation were reviewed for Achromobacter xylosoxidans and Stenotrophomonas maltophilia and their antibiotic susceptibility patterns. Bacteria were defined as pan-resistant if they were resistant or intermediate to all antibiotics tested; otherwise, organisms were defined as MDR. Patients were divided into 5 groups: pan-resistant Achromobacter xylosoxidans (n = 9), MDR Achromobacter xylosoxidans (n = 15), pan-resistant Stenotrophomonas maltophilia (n = 5), MDR Stenotrophomonas maltophilia (n = 26), and CF patients without Achromobacter xylosoxidans, Stenotrophomonas maltophilia or Bulkholderia cenocepacia (n = 131). Survival was compared, and cause of death was described., Results: The survival was similar between all cohorts (P = 0.29). Recurrence of the primary pathogen was the most common with pan-resistant Achromobacter xylosoxidans (100%) followed by MDR Stenotrophomonas maltophilia (46%), MDR Achromobacter xylosoxidans (33%), and finally, pan-resistant Stenotrophomonas maltophilia (20%). Death attributable to the primary pathogen was uncommon, occurring in 2 patients with MDR Stenotrophomonas maltophilia and 2 patients with MDR Achromobacter xylosoxidans., Conclusions: The CF patients with Achromobacter xylosoxidans and Stenotrophomonas maltophilia have similar posttransplant survival as compared to other CF patients, irrespective of their antibiotic susceptibility patterns. The presence of these organisms should not preclude lung transplantation.

Background: Bezoars are concretions of ingested matter which accumulate in the gastrointestinal tract and manifest as symptomatic foreign bodies. The aim of this study is to evaluate the incidence of gastric bezoars after lung transplantation and identify associated risk factors., Methods: We performed a retrospective analysis of patients who underwent lung transplantation from December, 1992 through July, 2005 at our tertiary care medical center. Patients who had endoscopically confirmed gastrointestinal bezoars in the posttransplant setting were identified and compared with patients without bezoars., Results: Of the 215 patients who received lung transplantation, 17 (7.9%) developed gastric bezoars confirmed by upper endoscopy. Cystic fibrosis was the leading indication for lung transplantation (n=145), and 11% of cystic fibrosis patients (16 of 145) formed gastric bezoars after transplant. Additionally, 94% of patients with bezoars (16 of 17) had cystic fibrosis (P=0.02), with the exception being a subject with primary ciliary dyskinesia. No patient who underwent lung transplant for another indication was found to have a bezoar. The mean time to diagnosis was 34 days, with two-thirds of bezoars diagnosed within one month after transplant. The annual incidence was unchanged during the study period., Conclusions: Gastric bezoars are common in cystic fibrosis patients after lung transplantation. The etiology is likely multifactorial, related to gastric motility, respiratory secretions, and medications. Further investigation is needed to understand the pathogenesis of bezoar formation in this selected population, and strategies for primary prevention may be beneficial.

More effective immunosuppressants are needed to improve lung-transplantation survival. PX3.102 is a novel immunosuppressant isolated from a mixture of traditional Chinese herbs. We tested its protective role on chronic lung rejection in the heterotopic tracheal transplant model. C57BL/6 mice received BALB/c tracheal grafts and were treated with PX3.102, cyclosporine A, or vehicle. PX3.102 improved tracheal allograft lumen patency (*P<0.01 vs. vehicle and P=0.14 vs. cyclosporine A) but not epithelialization (P>0.2 vs. vehicle). Subsequent in vitro studies demonstrated that PX3.10 was toxic to fully differentiated human tracheal epithelial cells in a dose-dependent manner. PX3.102 markedly suppressed antigen-specific lymphocyte proliferation in vitro at a concentration 10 times lower than cyclosporine A. In conclusion, PX3.102, a promising and potent immunosuppressant, although exhibiting toxicity to airway epithelial cells at high doses, is effective in inhibiting chronic airway allograft rejection.

Background: Obliterative bronchiolitis (OB), chronic allograft rejection of the lung, is a major cause of morbidity and mortality after lung transplantation. Previous studies using the heterotopic mouse trachea model of chronic airway rejection have shown a T cell infiltrate composed of CD4+ and CD8+ T cells. The goal of these experiments was to characterize the pattern of T lymphocyte cytokines during chronic airway rejection using the heterotopic mouse trachea model., Methods: Isografts (BALB/c into BALB/c) and allografts (BALB/c into C57BL/6) were implanted into cyclosporin-treated animals and harvested 2, 4, 6, and 10 weeks posttransplant. Cytokine mRNA expression in these grafts was determined using reverse transcription polymerase chain reactions. Expression of Th1 cytokines, interleukin- (IL) 2 and gamma-interferon, and Th2 cytokines, IL-4, and IL-10 were analyzed, as well as the cytotoxic lymphocyte product granzyme B and expressed relative to beta-actin gene expression., Results: In allografts, expression of IL-2 (P=0.002), gamma-interferon (P=2x10(-6)), granzyme B (P=0.003), IL-4 (P=0.06), and IL-10 (P=8x10(-6)) were 2- to 10-fold higher compared to isografts throughout the time-course of graft injury. Th1 and cytotoxic lymphocyte gene expression were increased to a greater extent than Th2 cytokines in allografts compared with isografts, and both Th1 and Th2 cytokine gene expression persisted at 6-10 weeks., Conclusions: These data suggest that Th1, Th2, and cytotoxic lymphocyte subtypes all contribute to the development of obliterative bronchiolitis in the heterotopic mouse trachea model. Efforts to reduce the development of obliterative bronchiolitis may require the antagonism of multiple T cell pathways.

Pulmonary thrombus formation in the region of atrial anastomosis following lung transplantation has been reported by several authors. Such patients typically present immediately after surgery with significant hemodynamic compromise causing pulmonary edema and hypoxemia. We describe a patient who presented with bilateral neurologic deficits 4 and 6 weeks after lung transplantation. Despite a normal transthoracic echocardiogram, transesophageal echocardiography (TEE) detected a large left atrial thrombus adherent to the atrial anastomosis. This thrombus was treated with intravenous heparin and subsequently warfarin. After 3 weeks, a repeat TEE demonstrated complete resolution of the lesion. This case demonstrates that postoperative left atrial and pulmonary venous thrombi may provide the basis for serious patient morbidity without hemodynamic or radiographic clues to their presence, that TEE is superior to transthoracic echocardiography for detecting left atrial thrombi, and that such lesions can respond to medical management alone.

Current United Network for Organ Sharing policy requires listing lung transplant recipients with an acceptable donor weight range, but lung size is a function of height, age, sex, and race. Frequently, lung transplant recipients are underweight, which results in a large discrepancy between donor and recipient weights. We reviewed our experience with size discrepancy between donors (D) and recipients (R) of 49 double-lung transplant (DLTX) procedures since July 1990. Pneumoreduction procedures were performed in 11 recipients of lungs judged to be too large at the time of DLTX (right middle lobectomy, 2; lingulectomy, 2; both, 6; right middle lobectomy and bilateral apical resections, 1). Predicted forced vital capacity (FVC) and total lung capacity (TLC) of donors and recipients were calculated. Donors were larger than recipients in general (D:R height = 1.02; D:R weight = 1.46), and, as a result, recipient-predicted lung volumes were smaller than donor-predicted lung volumes (D:R FVC = 1.1; D:R TLC = 1.1). Recipients undergoing pneumoreduction procedures had a significantly greater size discrepancy between donors and recipients; thus, both the ratio of D:R and the difference between D and R predicted FVC and TLC were significantly greater among recipients who underwent pneumoreduction, compared with nonreduced recipients. For recipients in the pneumoreduction group, predicted FVC and TLC were recalculated, with a proportionate amount subtracted based on the number of pulmonary segments removed. When the "corrected" FVC and TLC of the donors were compared with recipient-predicted FVC and TLC, there was no longer any significant difference between reduced and non-reduced groups, which implies that visual estimate of size mismatch at surgery is an accurate measure of size discrepancy. Post-DLTX spirometry showed identical improvement in FVC in patients who had pneumoreduction and those who did not, and survival at 6 months was identical in both groups. We conclude that pneumoreduction had no adverse effect on survival or post-DLTX spirometry, allowing safe use of larger donors in small recipients. Also, because lung size is more a function of height than weight, this study challenges the United Network for Organ Sharing practice of listing recipients with an acceptable donor weight range.