Pulmonary dysfunction after lung transplantation: the dilemma of coexisting mitral regurgitation.

A case of MR progression after single-lung transplant as a significant contributor to postoperative respiratory failure is reported. Pre-existing MR may progress due to the decompressive effects of lung transplantation on RV dimension and consequent alteration of MV geometry. This case highlights the importance of intraoperative TEE findings, especially pertaining to valvulopathies in the setting of lung transplantation. Postoperative surveillance of significant findings is imperative when any new symptoms are being investigated.

Single-lung transplantation in the United States: what happens to the other lung?

BACKGROUND: This study assessed treatment patterns and examined organ utilization in the setting of single-lung transplantation (SLT). METHODS: The United Network for Organ Sharing database was queried for all SLTs performed from 1987 to 2011. Trends in utilization of the second donor lung were assessed, both from recipient and donor perspectives. Donors were stratified into 2 groups: those donating both lungs and those donating only 1 lung. Independent predictors of using only 1 donor lung were identified using multivariable logistic regression. RESULTS: We identified 10,361 SLTs originating from 7,232 unique donors. Of these donors, both lungs were used in only 3,129 (43.3%), resulting in more than 200 second donor lungs going unused annually since 2005, with no significant increase in use over time (p = 0.95). After adjustment, donor characteristics predicting the second donor lung going unused included B/AB blood groups (adjusted odds ratio [AOR]: 1.69 and 2.62, respectively; p < 0.001), smaller body surface area (AOR, 1.30; p = 0.02), lower donor partial pressure of arterial oxygen (AOR, 0.90 per 50 mm Hg increase; p < 0.001), pulmonary infection (AOR, 1.15; p = 0.04), extended criteria donor status (AOR, 1.66; p < 0.001), and death caused by head trauma (AOR, 1.57; p < 0.001) or anoxia (AOR, 1.53; p = 0.001). CONCLUSIONS: Among donors for SLT, less than half of all cases led to use of the second donor lung. Although anatomic, infectious, or other pathophysiologic issues prohibit 100% utilization, more aggressive donor matching efforts may be a simple method of increasing the utilization of this scarce resource, particularly for less common blood types.

Determining eligibility for lung transplantation: A nationwide assessment of the cutoff glomerular filtration rate.

BACKGROUND: Historical concerns about lung transplantation in patients with a glomerular filtration rate (GFR) ≤ 50 ml/min/1.73 m(2) have not been validated. We hypothesize that a pre-transplant GFR ≤ 50 ml/min/1.73 m(2) represents a high mortality risk, especially in the setting of acute GFR decline. In addition, we explore the potential for improved risk stratification using a statistically derivable alternative cutoff. METHODS: Adult, primary, lung recipients in the United Network for Organ Sharing database were analyzed (October 1987 to December 2011). Recursive partitioning identified the GFR value that provides maximal separation in 1-year mortality. Survival over/under the cutoffs was compared using stratified log-rank, Cox, and Kaplan-Meier methods, before and after 1:2 propensity score matching. RESULTS: Median GFR at time of transplant for 19,425 study patients was 94.2 ml/min/1.73 m(2) (quartile 1-quartile, 2 76.9-105.9 ml/min/1.73 m(2)). Recursive partitioning identified a GFR of 40.2 ml/min/1.73 m(2) as the ideal inflection point for predicting 1-year survival. Cutoffs demonstrated statistically significant effects on survival after 840 patients with a GFR ≤ 50 ml/min/1.73 m(2) (hazard ratio, 1.28; 95% confidence interval, 1.15-1.43) and 401 patients with a GFR ≤ 40.2 ml/min/1.73 m(2) (hazard ratio, 1.57; 95% confidence interval, 1.36-1.83) were matched with high GFR controls (p < 0.001). In 13,509 patients with available GFR at the time of listing and transplant, a pre-transplant GFR decline of ≥ 50% from baseline was associated with worse survival (p < 0.001). CONCLUSIONS: A pre-transplant GFR ≤ 50 ml/min/1.73 m(2) is associated with decreased survival. However, patients with GFR between 40 and 50 ml/min/1.73 m(2) do not suffer excessive post-transplant mortality and should not be automatically excluded from listing. Notably, outcomes are worse in patients with poor renal function and concomitant pre-transplant GFR decline. Strategies should be devised to detect and manage interval renal deterioration before lung transplantation.

Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients.

BACKGROUND: Aerosolized administrations of amphotericin B deoxycholate (AmBd) and amphotericin B lipid complex (ABLC) in lung transplant recipients were compared for safety and tolerability. The incidence of invasive fungal infections in patients receiving aerosolized amphotericin B formulations as sole prophylaxis was determined. METHODS: A prospective, randomized (1:1), double-blinded trial was conducted with 100 subjects. AmBd and ABLC were administered postoperatively by nebulizer at doses of 25 mg and 50 mg, respectively, which were doubled in mechanically ventilated patients. The planned treatment was once every day for 4 days, then once per week for 7 weeks. Treatment-related adverse events and invasive fungal infections were quantitated for 2 months after study drug initiation. RESULTS: Intent-to-treat analysis revealed study drug was discontinued for intolerance in 6 of 49 (12.2%) and 3 of 51 (5.9%) patients in the AmBd- and ABLC-treated groups, respectively (p=0.313). Subjects receiving AmBd were more likely to have experienced an adverse event (odds ratio 2.16, 95% confidence interval 1.10, 4.24, p=0.02). Primary prophylaxis failure within 2 months of study drug initiation was observed in 7 of 49 (14.3%) AmBd-treated patients and 6 of 51 (11.8%) ABLC-treated patients. No fungal pneumonias were observed. Only two (2%) patients experienced documented primary prophylaxis failure with Aspergillus infections within the follow-up period. CONCLUSIONS: Both aerosol AmBd and ABLC appear to be associated with a low rate of invasive pulmonary fungal infection in the early posttransplant period. Patients receiving ABLC were less likely to experience a treatment-related adverse event.

The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation best characterizes kidney function in patients being considered for lung transplantation.

BACKGROUND: Methods for direct measurement of glomerular filtration rate (GFR) are expensive and inconsistently applied across transplant centers. The Modified Diet in Renal Disease (MDRD) equation is commonly used for GFR estimation, but is inaccurate for GFRs >60 ml/min per 1.73 m(2). The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) and Wright equations have shown improved predictive capabilities in some patient populations. We compared these equations to determine which one correlates best with direct GFR measurement in lung transplant candidates. METHODS: We conducted a retrospective cohort analysis of 274 lung transplant recipients. Pre-operative GFR was measured directly using a radionuclide GFR assay. Results from the MDRD, CKDEPI, Wright, and Cockroft-Gault equations were compared with direct measurement. Findings were validated using logistic regression models and receiver operating characteristic (ROC) analyses in looking at GFR as a predictor of mortality and renal function outcomes post-transplant. RESULTS: Assessed against the radionuclide GFR measurement, CKDEPI provided the most consistent results, with low values for bias (0.78), relative standard error (0.03) and mean absolute percentage error (15.02). Greater deviation from radionuclide GFR was observed for all other equations. Pearson's correlation between radionuclide and calculated GFR was significant for all equations. Regression and ROC analyses revealed equivalent utility of the radionuclide assay and GFR equations for predicting post-transplant acute kidney injury and chronic kidney disease (p < 0.05). CONCLUSIONS: In patients being evaluated for lung transplantation, CKDEPI correlates closely with direct radionuclide GFR measurement and equivalently predicts post-operative renal outcomes. Transplant centers could consider replacing or supplementing direct GFR measurement with less expensive, more convenient estimation by using the CKDEPI equation.

Cromolyn ameliorates acute and chronic injury in a rat lung transplant model.

BACKGROUND: Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown. METHODS: In this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control. RESULTS: The acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected. CONCLUSIONS: These findings provide impetus for further studies aimed at elucidating the effects of cromolyn and the role of mast cells in pulmonary allotransplantation.

Pulmonary xenotransplantation: rapidly progressing into the unknown.

As one approach to circumventing the dire shortage of human lungs for transplantation, a handful of investigators have begun to probe the possibility of pulmonary xenotransplantation. The immunologic and perhaps physiologic barriers encountered by these investigators are considerable and progress in pulmonary xenotransplantation has lagged behind progress in cardiac and kidney xenotransplantation. However, during the last few years there have been substantial advances in the field of pulmonary xenotransplantation including, most noticeably, significant progress in attenuating hyperacute dysfunction. Progress has been made in understanding the barriers imposed by xenoreactive antibodies, complement, coagulation incompatibility and porcine pulmonary intravascular macrophages. Although our understanding of the barriers to pulmonary xenotransplantation is far from complete and the clinical application of pulmonary xenotransplantation is not yet in sight, current progress is fast paced. This progress provides a basis for future work and for a hope that the shortage of human lungs for transplantation will not always be a matter of life and death.

Delay of CMV infection in high-risk CMV mismatch lung transplant recipients due to prophylaxis with oral ganciclovir.

Cytomegalovirus (CMV) is a common opportunistic infection in lung transplant recipients. Despite the use of early post-operative intravenous ganciclovir, most high-risk patients develop CMV infection. We conducted this retrospective study to determine the efficacy of extended CMV prophylaxis with oral ganciclovir in high-risk, donor-positive-recipient-negative, lung recipients. All patients initially received 3 months of intravenous ganciclovir and CMV hyperimmune globulin. Clinical outcomes in all CMV mismatch patients undergoing lung transplant surviving at least 3 months were included (n = 42). Since 1998, 14 patients received no oral ganciclovir prophylaxis (group 1) and 28 patients received indefinite oral ganciclovir after completion of intravenous therapy (group 2). In those patients receiving oral ganciclovir, the prevalence of post-transplant CMV infection was significantly reduced over the first 180 d post-transplant (50% in group 1 vs. 4% in group 2; p < 0.001). Although some CMV events were observed with additional follow-up in group 2, there remained a significantly greater freedom from CMV infection by Kaplan-Meier analysis in group 2 as compared with group 1, with over 30 months follow-up time in each group (log-rank, p = 0.02). A moderate rate of drug discontinuation was observed in group 2, and no severe drug-related events occurred. In high-risk lung transplant recipients, CMV prophylaxis with intravenous ganciclovir, followed by indefinite oral ganciclovir, significantly delays and reduces post-transplant CMV infections. A larger prospective randomized study is needed to confirm the benefits of oral ganciclovir on CMV prevention.

Gastroesophageal reflux disease in lung transplant recipients.

BACKGROUND: Chronic allograft dysfunction after lung transplantation contributes to poor long-term survival. A link between gastric aspiration and post-transplant lung dysfunction has been suggested, but little is known about the significance of gastroesophageal reflux disease (GERD) after lung transplantation. METHODS: A retrospective study was performed to determine the prevalence of GERD in lung transplant recipients. Patients who underwent lung transplantation at Duke University, survived at least 6 months and had post-transplant 24-h pH studies were included in the analysis. Antireflux medications were discontinued prior to the pH study. Demographic data, pH study date and results, FEV1 at the time of the pH study, confirmed acute rejection episodes, and current medications were collected. The FEV1 ratio was calculated at the time of pH study (current FEV1/best post-transplant FEV1). RESULTS: Forty-three patients met entry criteria. Studies were performed at a median of 558 d post-transplant. Thirty of forty-three (69.8%) patients tested had abnormal total acid contact times (normal: <5%). The mean acid contact times for all patients were 10% total, 11.8% upright and 7.9% supine. A negative correlation was found between total or upright acid reflux and FEV1 ratio at the time of studies (-0.341 and -0.419; p = 0.025 and p = 0.005, respectively). The effect of acid reflux on FEV1 ratio remained significant after multivariable analysis. CONCLUSIONS: There is a high prevalence of GERD among selected lung transplant recipients who had pH studies performed and its presence is associated with worse pulmonary function. Future studies are needed to assess whether GERD contributes to the pathogenesis of bronchiolitis obliterans syndrome (BOS).