Double-lung Recipients Research Articles

Effects of donor smoking history on early post-transplant lung function measured by oscillometry.

Prior studies assessing outcomes of lung transplants from cigarette-smoking donors found mixed results. Oscillometry, a non-invasive test of respiratory impedance, detects changes in lung function of smokers prior to diagnosis of COPD, and identifies spirometrically silent episodes of rejection post-transplant. We hypothesise that oscillometry could identify abnormalities in recipients of smoking donor lungs and discriminate from non-smoking donors. This prospective single-center cohort study analysed 233 double-lung recipients. Oscillometry was performed alongside routine conventional pulmonary function tests (PFT) post-transplant. Multivariable regression models were constructed to compare oscillometry and conventional PFT parameters between recipients of lungs from smoking vs non-smoking donors. The analysis included 109 patients who received lungs from non-smokers and 124 from smokers. Multivariable analysis identified significant differences between recipients of smoking and non-smoking lungs in the oscillometric measurements R5-19, X5, AX, R5z and X5z, but no differences in %predicted FEV1, FEV1/FVC, %predicted TLC or %predicted DLCO. An analysis of the smoking group also demonstrated associations between increasing smoke exposure, quantified in pack years, and all the oscillometry parameters, but not the conventional PFT parameters. An interaction was identified between donor-recipient sex match and the effect of smoking. The association between donor smoking and oscillometry outcomes was significant predominantly in the female donor/female recipient group.

Association Between FEV₁ Decline Rate and Mortality in Long-Term Follow-Up of a 21-Patient Pilot Clinical Trial of Inhaled Liposomal Cyclosporine Plus Standard-of-Care Versus Standard-of-Care Alone for Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND The association between forced expiratory volume in 1 second (FEV1) trajectory and mortality in bronchiolitis obliterans syndrome (BOS) is not well defined. Using long-term data from a prior clinical trial of inhaled liposomal cyclosporine A (L-CsA-I) for lung transplant patients with BOS, this study examined the association between longitudinal FEV₁ change and mortality. MATERIAL AND METHODS We analyzed long-term data from a clinical trial which randomized 21 patients with BOS (³20% decrease in FEV1 from personal maximum) to receive L-CsA-I plus standard-of-care (n=11) or standard-of-care (SOC) alone (n=10) for 24 weeks. A joint statistical model, combining a linear mixed model for FEV₁ change and Cox regression for mortality, was utilized to examine the overall association between FEV₁ trajectory and mortality during follow-up. RESULTS The 21 trial participants (10 single, 11 double lung recipients) had a mean FEV₁ of 1.7±0.6 Liters at randomization. Median follow-up post-randomization was 35 months. In joint model analysis, 1 percent FEV₁ decline predicted 1.076-fold increased mortality risk (95% confidence interval: -0.998 to 1.160, p=0.058). FEV₁ decline was reduced by 2.6% per year in L-CsA-I patients compared to SOC (p=0.210), and overall survival at 1/3/5 years was 91%/64%/27% vs 90%/20%/0% for L-CsA-I versus SOC, respectively (p=0.164). CONCLUSIONS In BOS patients, greater longitudinal FEV₁ decline predicts increased mortality. Trends towards prolonged stabilization of FEV₁ and improved survival were observed with L-CsA-I receipt. Further analyses will aid in evaluating the utility of FEV₁ change as a survival predictor, having implications in BOS management and future trial design.

(1188) Assessment of Dd-cfDNA Between Stable Single and Double Lung Recipients

(1188) Assessment of Dd-cfDNA Between Stable Single and Double Lung Recipients

Comparative Influence of Primary Healthcare Payer Types on Patient Outcomes After Lung Transplantation

<h3>Purpose</h3> Optimal outcomes in patients undergoing lung transplantation requires significant utilization of resources. We, therefore, evaluated the association of primary payer type with outcomes after lung transplantation. <h3>Methods</h3> Using the UNOS (United Network for Organ Sharing) registry we studied 15129 first-time lung transplant recipients from January 2000 to December 2017 and compared all-cause mortality at 1 year. Single lung (N=4524) and double lung (N=10605) recipients were subgrouped by payer type: Medicaid (32% and 27% respectively), Medicare (26% and 18%), and commercial insurance (42% and 54%). <h3>Results</h3> Primary payer type was not significantly associated with inferior outcomes at 1 year following both single-lung (P=0.447) and double lung transplant (P=0.531). Insurance was also not a predictor of worse outcomes following single lung transplant after 3 years (P=0.107). However, insurance type was associated with different outcomes in double lung recipients at 3 years (P=0.028) and remained significant predictors of early mortality after adjustment for covariates in multivariate Cox proportional hazard ratio analyses (P<0.05). <h3>Conclusion</h3> These data are among the first to provide insight into the impact of insurance status on patient outcomes for a modern cohort of lung transplant recipients. All-cause mortality after single-lung and double-lung transplantation did not differ significantly by payer type after 1 year. However, primary payer type was associated with 3-year outcomes following double lung transplant. More research is needed to confirm and define the reasons for insurance type playing a role in outcomes after double lung transplant as compared to single lung transplant.

Adult Lung Transplantation from Donation After Circulatory Death Donors: Safety and Outcomes Utilizing the UNOS / OPTN Registry

<h3>Purpose</h3> Donation after circulatory death (DCD) has been described in abdominal transplantation but has not been thoroughly evaluated in lung transplantation. The aim of this retrospective study was to describe and compare DCD utilization with donation after brain death (DBD). <h3>Methods</h3> The United Network for Organ Sharing (UNOS) database was reviewed for all adult patients who underwent lung transplant between 2016 and 2020. Baseline features and post-transplant outcomes were reviewed using descriptive and survival analyses by the Kaplan-Meier and Cox regression method. <h3>Results</h3> A total of 11,837 isolated lung transplant recipients met criteria for analysis. DCD utilization increased over time, from 92/2198 (14.7%) in 2016 to 180/2376 (28.8%) recipients in 2020 (p<0.001 for trend). DCD patients were more likely double lung recipients (79.9 vs 74.6%), had longer ischemia times (7.6 vs. 5.5 h), and were more commonly intubated (42.8 vs. 29.9%) and required extracorporeal support (12.5 vs 7.2%) up to 72 h following surgery (Table 1). Unadjusted overall survival was worse for DCD vs DBD patients (log rank, p<0.001). When stratified by transplant type, there was no survival difference between DCD and DBD single lung recipients (log rank, p=0.322); however, survival among double lung recipients was worse for DCD vs DBD patients (log rank, p<0.001). After adjustment for statistically significant covariates (Table 1), DCD status was not associated with mortality for double lung recipients (HR: 1.189, 95% CI [0.985 - 1.435]; p=0.071). Ischemia time (HR: 1.029, 95% CI [1.007 - 1.052]; p=0.010) and extracorporeal support (HR: 2.862, 95% CI [2.512 - 3.260]; p<0.001) after transplant were more common in DCD patients and strongly associated with mortality up to 5 years. <h3>Conclusion</h3> DCD status was associated with worse survival in double lung transplant recipients, which may be attributed to longer ischemia times. Additional efforts will be required to characterize and mitigate these effects.

Azithromycin prophylaxis after lung transplantation is associated with improved overall survival

Azithromycin prophylaxis (AP) in lung transplant recipients has been shown to reduce the composite end-point of death or chronic lung allograft dysfunction (CLAD) onset but without a clear effect on overall survival. Our program began using AP in 2010. We sought to evaluate the association between AP and survival and the risk of CLAD and baseline lung allograft dysfunction (BLAD). We studied double lung recipients transplanted between 2004 and 2016. We defined AP as chronic use of azithromycin initiated before CLAD onset. We analyzed the association between AP and death or retransplant using Cox regression with adjustment for potential confounders. We further used Cox and logistic models to assess the relationship between AP and post-transplant CLAD onset and BLAD, respectively. A total of 445 patients were included, and 344 (77%) received AP (median time from transplant: 51 days). Patients receiving AP were more likely to receive induction with interleukin-2 receptor antagonists (57% vs 35%; p < 0.001). AP was associated with improved survival (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42-0.82; p = 0.0020) in our fully adjusted model, with a reduced adjusted risk of BLAD (odds ratio: 0.53; 95% CI: 0.33-0.85; p = 0.0460) but no clear reduction in the adjusted risk of CLAD (HR: 0.69; 95% CI: 0.47-1.03; p = 0.0697). AP is associated with improved survival after lung transplantation, potentially through improved baseline function. These findings build on prior trial results and suggest that AP is beneficial for lung transplant recipients.

Right single lung transplantation or double lung transplantation compared with left single lung transplantation in chronic obstructive pulmonary disease

Although single and double lung transplantation outcomes for chronic obstructive pulmonary disease (COPD) have been investigated, right and left single lung transplants have never been rigorously compared to evaluate disease-specific differences. Single lung transplants for COPD often have hyperinflation of the contralateral native lung, which may be more pronounced in left lung transplants. Using the United Network for Organ Sharing registry, we conducted a retrospective cohort study of 5,585 adults who underwent lung transplantation for COPD from May 4, 2005 to June 30, 2017. Subjects were followed until March 2019. Post-transplant survival was compared using Cox proportional hazards and Royston and Parmar's flexible parametric survival models. We adjusted for donor and recipient factors with known or plausible associations with survival. Lung transplant recipients who received a left single lung transplant for COPD had an increased risk of post-transplant death when compared with those who received a right single lung transplant for COPD (hazard ratio [HR]: 1.24, 95% CI: 1.08-1.48, p = 0.002). Survival did not differ significantly between double lung transplant and right single lung transplant recipients (HR: 0.88, 95% CI: 0.77-1.02, p = 0.086). Adjusted 5-year survival was 57.8% (95% CI: 55.7-60.1) for double lung recipients, 56.7% (95% CI: 55.4-58.0) for right single lung recipients, and 50.9% (95% CI: 47.2-55.0) for left single lung recipients. In COPD, right single lung transplantation was associated with improved post-transplant survival compared with left single lung transplantation, and no significant difference in post-transplant survival compared with double lung transplantation was found. In light of the ongoing donor lung shortage, preferential allocation of right single lungs to patients with COPD should be considered.

Suboptimal Donors Do Not Mean Worse Results: A Single-Center Study of Extending Donor Criteria for Lung Transplant

BackgroundLung transplant remains the only viable treatment for most of the end-stage lung diseases. It is believed that extending criteria for donor lungs would increase the number of lung transplants. The aim of the study was to compare the graft function by means of oxygenation index among recipients who received the lungs from donors of extended criteria with those whose received lungs from donors who met the standard criteria. MethodsThis retrospective study analyzed 71 donors whose lungs where transplanted into 71 first-time double lung recipients of 2 groups: patients who received transplants before and after 2018. The objective was to assess whether there is a significant difference in quality of the donor pool after applying extended criteria. The second objective was to compare results of recipients with lungs from donors of oxygenation index > 400 mm Hg with those obtained among recipients with this parameter < 400 mm Hg. ResultsIn the case of transplants performed in 2018 to 2019, oxygenation indices were significantly lower in donors but significantly higher in recipients on the first day than those observed in 2015 to 2017. The number of transplants increased from 9 per year to 22 per year. Irrespective of whether the donor had PaO2/fraction of inspired oxygen above or below 400 mm Hg, recipients showed similar oxygenation index values after transplant (mean oxygenation index, 462 vs 412 mm Hg, respectively). Short-term mortality did not differ either. ConclusionsExtended criteria of lungs suitability as a potential grafts not only increases the donor pool but also proves that suboptimal donors are not associated with producing inferior results of the recipients.

Single Lung Transplant vs Double Lung Transplant: A Single-Center Experience With Particular Consideration for Idiopathic Pulmonary Arterial Hypertension

BackgroundLung transplant remains the only viable treatment for certain patients with end-stage lung diseases. Such patients can become either single or double lung recipients. The 2 procedures are associated with specific risks and benefits. The aim of the study was to assess the survival of patients after lung transplant in a single center. MethodsThe retrospective study consists of 128 lung transplant recipients. Patients underwent transplant between 2004 and 2017 because of following diseases: chronic obstructive pulmonary disease (28.2%), cystic fibrosis (26.5%), and primary pulmonary hypertension (12.3%), including idiopathic pulmonary arterial hypertension and interstitial lung diseases (33%). Patients with idiopathic pulmonary arterial hypertension were not treated with postoperative extracorporeal membrane oxygenation as left heart conditioning. ResultsRegardless of underlying disease, 75% of DLT recipients and 51% of SLT recipients reached 5-year survival (P = .0066). A total of 87% of lung transplant recipients with cystic fibrosis reached 1-year survival. Among lung recipients with primary pulmonary hypertension who underwent DLT and SLT, 5-year survival was reached by 84% and 51%, respectively (P = .025). Among patients with chronic obstructive pulmonary disease, 82% of DLT recipients and 62% of SLT recipients reached 1-year survival (P = .22). Patients who received transplants because of primary pulmonary hypertension presented the worst short-term survival among all SLT recipients. ConclusionsPatients with CF have the best overall survival among all lung transplant recipients. Double lung transplant provides statistically significantly better outcomes than single lung transplant. This observation is also present among recipients who underwent transplant because of primary pulmonary hypertension, as single lung transplant is not recommended among such patients in particular.

Impact of Cold Ischemia Time on Frequency of Airway Complications Among Lung Transplant Recipients

BackgroundThe cold ischemia time (CIT) is a period of time between harvesting an organ for transplant and its reperfusion just after implantation. CIT may have an impact on frequency of complications after lung transplant that can be treated by means of bronchoscopic intervention. The aim of the study was to investigate the correlation between CIT and frequency of bronchoscopic intervention. MethodsThe retrospective study consists of 91 patients: 22 single lung recipients (24%) and 69 double lung recipients (76%) who underwent lung transplant from March 2012 to June 2019. All statistical analyses were performed in SPSS 25.0 and R 3.5.3. The P levels less than .05 were deemed statistically significant. ResultsThe average CIT in single lung transplant was 5.91 hours, and in double lung transplant it was 8.61 hours. For the 4- to 8-hour CIT the percentages were 80.95% for single lung recipients and 46.38% for double lung recipients. For CIT longer than 8 hours, the following percentages were observed: 9.53% in single lung transplant and 53.62% in double lung transplant. Each subsequent hour of CIT exponentially increases the risk of intervention 1505 times (50.05%). ConclusionsProlonged CIT seems to be a risk factor for airway complication, especially in the double lung recipient group.

Early protein expression profile in bronchoalveolar lavage fluid and clinical outcomes in primary graft dysfunction after lung transplantation.

Primary graft dysfunction (PGD) remains a major post-transplant complication and is associated with increased morbidity and mortality. Mechanisms evoking PGD are not completely clear, but inflammation plays a central role. We investigated the association between PGD and inflammatory proteins present in immediate postoperative bronchoalveolar lavage. All double-lung recipients transplanted at our institution from 2002 to 2018 were included in our study. We retrospectively selected 80 consecutive lung transplant recipients with different PGD grades (n = 20 for each PGD grades 0-1 to 2-3). In bronchoalveolar lavage performed within the first 24 h after donor aortic cross-clamping following lung transplantation, concentrations of 30 cytokines, chemokines and growth factors were assessed by enzyme-linked immunosorbent assay (ELISA) and correlated with donor and recipient demographics and outcomes. For analysis, 2 groups were defined: 'mild' PGD (grade 0-1) and 'severe' PGD (grades 2-3). Significant differences between mild and severe PGD were found in 8 biomarkers [interleukin (IL)-6, IL-10, IL-13, eotaxin, granulocyte colony-stimulating factor, interferon γ, macrophage inflammatory protein 1α, surfactant protein D (SP-D); P < 0.05]. Increased IL-10 and IL-13, but none of the other proteins, were associated with short-term outcome (longer time to extubation; P = 0.005 and P < 0.0001; increased intensive care unit stay; P = 0.012 and P < 0.0001; and hospital stay; P = 0.041 and P = 0.002). There were no significant differences in donor and recipient characteristics between the groups. Expression profiles of key inflammatory mediators in bronchoalveolar lavage fluid differed significantly between lung transplant recipients with severe versus mild PGD and correlated with clinical outcome variables. Further research should focus on the early mechanisms leading to PGD.

Disparities in the Lung Allocation Score Due to Geography Have Not Changed Since November 2017

Differences in geographic donor lung availability affect waitlist outcomes. We hypothesized that the lung allocation score (LAS) at transplant and waitlist time would vary based on local donor lung availability and that broader geographic sharing since November 2017 would improve these disparities. Using UNOS data, we conducted a retrospective cohort study of 23,414 lung transplant recipients from January 1, 2006 - December 31, 2018. Local lung availability was defined as the ratio of donor lungs to waitlist candidates in the local donation service area. We calculated the local lung availability for candidates prior to November 25, 2017. We used mixed multivariable linear regression and Poisson regression, adjusting for time dependent LAS changes, to examine the relationship between local lung availability, LAS at transplant and waitlist time. We used Wilcoxon rank-sum to compare LAS at transplant before and after November 2017. Compared to recipients in the top quartile with greatest local lung availability, recipients in the lowest quartile were transplanted with a LAS 6.2 points higher (95% CI: 5.6-6.9, p <0.001) and waited significantly longer, 186 days (95% CI: 178-194) compared with 93 days (95%CI: 88-97), p <0.001. This difference varied by transplant type, with single lungs recipients transplanted with a LAS 2.0 points higher in the lowest quartile (95%CI: 0.9-3.0, p < 0.001) compared with the top and double lung recipients transplanted with a LAS 8.8 points higher (95% CI: 8.0-9.6, p<0.001) in the lowest quartile compared with the top. At centers in the lowest quartile of local lung availability, the LAS at transplant did not meaningfully change after November 2017 (44.1 ± 15.2, compared to 45.7± 16.3, p=0.042), however the waitlist time did decrease from 206 days (95%CI: 192-222) to 155 days, (95% CI: 133-176), p <0.001. The LAS at transplant and waitlist time for recipients did not change at high local lung availability centers (50.7 ± 19.6 compared to 51.3 ± 19.6, p=0.38, and 74 days (95%CI: 66-81) compared to 61 days (95%CI: 52-70), p=0.66). Prior to November 2017, low local lung availability was associated with longer waitlist times and higher LAS at transplant that were much more pronounced for double lung recipients. Since expanding allocation to 250 miles, meaningful differences in LAS at transplant have not yet been observed.

Long term survival after lung transplantation: A single center experience

There are approximately 2000 lung transplants performed across the United States annually. There is limited data to identify factors predictive of long-term survival. We evaluated 10-year survivors after lung transplant to determine predictors of long-term survival. Data were collected from the United Network for Organ Sharing registry database from a single institution. Inclusion criteria were: patients who received a lung transplant between 1989 and 2005. Descriptive statistics were calculated, and survival outcomes were analyzed using the Kaplan-Meier method. Three hundred sixty-one patients received a lung transplant between 1989 and 2005, and 77 patients survived at least 10 years (21%). Diagnoses at the time of transplant included: chronic obstructive pulmonary disease/emphysema 45 (58.4%), idiopathic pulmonary fibrosis 12 (15.6%), alpha 1 anti-trypsin deficiency 6 (7.8%), cystic fibrosis 4 (5.2%), primary pulmonary hypertension 2 (2.6%), and Eisenmenger's syndrome 1 (1.3%). Seventy-four recipients (96.10%) were Caucasian; 46 (59.74%) were female. Age at the time of transplant ranged from 19 to 67 years (mean 50.8; median 52). Forty-two patients (54.5%) were double lung recipients. Survival ranged from 10.0 to 21.9 years (mean 15.5y; median 15.48y). Forty-two (54.5%) subjects are currently alive; the most common causes of death included: chronic rejection (20%), and infection (17.14%). Ten-year survivors were significantly younger, weighed less, and had significantly shorter lengths of hospitalization after transplantation. Bilateral lung transplantation was a significant factor in prolonged survival. Survival also improved with institutional experience.

(58) - Improvement in Frailty Is Associated with Improved Disability in Lung Transplantation

s S31 aims of this study were to investigate: 1) the changes in pectoralis muscle area (PMA) after lung transplant, and 2) the association between PMA and other anthropomorphic and clinical variables. Methods: We conducted a retrospective review of all patients undergoing lung transplantation at a single center between January 2009 and December 2014. Utilizing TomoVision Slice-O-Matic software, two independent examiners measured PMA on a single slice at the carina from CT scans of the thorax obtained pre-transplant and 6 and 12 months post-transplant. Single variable regression and Pearson’s correlations were performed to assess the relationship between PMA and clinical variables. Results: Of the 73 patients who underwent lung transplantation, the most common indications were interstitial lung disease (ILD, 60.3%), followed by chronic obstructive pulmonary disease (COPD, 24.7%) and cystic fibrosis (9.6%). Twenty-four patients (33%) underwent single lung transplant, while 49 (67%) had double lung transplant. Overall, neither body mass index (BMI) nor PMA changed at 6 or 12 months post-transplant (p= 0.89 and 0.08 respectively by repeated measures ANOVA). Pre-transplant diagnosis significantly influenced change in PMA. In patients with ILD, there was a decrease in PMA compared with those without ILD (-13.7±3.7% vs. 14.8±8.9%, p= 0.001). However, patients with COPD had increased PMA compared with those without COPD (15.4±11.3% vs. -10.5±3.8%, p= 0.008). In addition, single lung transplant patients showed an 8.4±8.3% increase in PMA, while double lung recipients had an 11.3±4.4% decrease (p= 0.03). Finally, % change in PMA at 12 months correlated with pre-transplant weight (ρ = -0.306, p= 0.04), pre-transplant BMI (ρ = -0.309, p= 0.04), and % change in BMI at 12 months (ρ = 0.625, p< 0.0001). Conclusion: Analysis of thoracic CT scans provides a convenient, accurate measure of changes in muscle mass in the post-lung transplant population and correlates with changes in BMI. Patients with COPD gain muscle mass following lung transplantation while patients with ILD lose muscle mass. The mechanisms underlying these changes need to be further investigated.

(628) - Is Routine Respiratory Viral PCR Testing in Lung Transplant Recipients Helpful?

Our unit adopted routine screening for a panel of respiratory viruses using quantitative PCR on all bronchoalveolar lavage (BAL) samples from LTx recipients since 2009. We evaluated diagnostic yield and usefulness of this approach. Retrospective examination of BAL viral PCR results in all LTx performed from January 2009 to December 2013 at our institution. Total number of samples and number of positive samples per patient were noted. Results were stratified by single (SLTx) vs. double (DLTx) lung recipients and by surveillance bronchoscopy (SB) vs. bronchoscopy clinically indicated by a drop in spirometry and/or radiographic changes (CB). 123 LTx were performed in the study period (35 SLTx, 88 DLTx; 70 males, mean age 52 yrs [range 17-65]; SLTx indications: IPF 25, other fibrosis 8, COPD 1, sarcoid 1; DLTx indications: CF 13, non-CF bronchiectasis 4, COPD 49, alpha 1 antitrypsin deficiency 8, obliterative bronchiolitis 3, IPF 2, other fibrosis 3, iPAH 4, CTEPH 1, sarcoid 1). Mean follow up was SLTx: 1001 days (range 10-2392) and DLTx 1034 (0-2344) during which 84 and 222 BAL viral PCR panels were performed respectively. 6 positive PCR results in 5 SLTx and 24 in 19 DLTx were noted (P=NS) at a median of 56 (range 40-845) vs 201 (range 3-1232) days post op (P=NS). Rhinovirus was most prevalent (18 samples vs. parainfluenza 6, adenovirus 4, respiratory syncytial virus 3, metapneumovirus 3). Rhinovirus co-existed with adenovirus in 2 patients and with parainfluenza in 1 patient. 7/228 (3%) SB vs 23/78 (29%) CB samples were PCR positive (P<0.05). Apart from 2 RSV episodes treated with oral ribavarin, no targeted therapy was implemented. Our data suggest a limited diagnostic yield from a respiratory viral PCR panel in routine surveillance BAL samples post LTx. Most viruses identified are self-limiting with no proven effective therapy and the cost of expensive routine testing is therefore unjustified. In contrast, clinically indicated BAL is 10 times more likely to reveal positive viral DNA. Freedom from respiratory viruses appeared numerically, though not statistically, shorter in SLTx recipients but this is confounded by the small sample size. Native lung factors may be relevant and this merits further investigation.

(770) - Donor Age and Ischemic Time Are the Only Marginal Donor Criteria That Effect Survival for Lung Transplantation

PurposeThis study examines post-transplantation survival in patients who underwent lung transplantation with marginal donor organs compared with non-marginal donor organs.MethodsThe United Network of Organ Sharing database was retrospectively analyzed from 2005 to 2013 to identify adult patients who underwent lung transplantation during the lung allocation score era. Marginal donor criteria included age ≥ 55 years old, gender mismatch, ischemic time > 6 hours, history of smoking > 20 pack years, abnormal chest X-ray, abnormal bronchoscopy, and arterial pO2 <350 mmHg on 100% FiO2. Kaplan-Meier analysis was used to compare actuarial survival. Cox regression analysis was used to further delineate significant factors impacting survival.ResultsThere were 10,242 patients who underwent lung transplantation during this time period, and 8895 (87.4%) patients received a marginal donor lung. 3-year survival was 65.7% and 66.7%, respectively, for those who received a marginal donor organ and those who did not (p=0.297). When stratified by single and double lung transplantation, survival was worse for patients who underwent marginal double lung transplantation (p=0.013). Cox regression analysis revealed age ≥ 55 years (p=0.034) and ischemic time >6 hours (p=0.026) as significant factors impacting survival for patients who underwent double lung transplantation. Survival curves for double lung recipients are shown in Figure 1.ConclusionDouble lung transplant recipients of marginal donor organs have worse 3-year survival when compared with recipients of non-marginal organs, but those poor outcomes appear to be driven by donors with advanced age and longer ischemic times. PurposeThis study examines post-transplantation survival in patients who underwent lung transplantation with marginal donor organs compared with non-marginal donor organs. This study examines post-transplantation survival in patients who underwent lung transplantation with marginal donor organs compared with non-marginal donor organs. MethodsThe United Network of Organ Sharing database was retrospectively analyzed from 2005 to 2013 to identify adult patients who underwent lung transplantation during the lung allocation score era. Marginal donor criteria included age ≥ 55 years old, gender mismatch, ischemic time > 6 hours, history of smoking > 20 pack years, abnormal chest X-ray, abnormal bronchoscopy, and arterial pO2 <350 mmHg on 100% FiO2. Kaplan-Meier analysis was used to compare actuarial survival. Cox regression analysis was used to further delineate significant factors impacting survival. The United Network of Organ Sharing database was retrospectively analyzed from 2005 to 2013 to identify adult patients who underwent lung transplantation during the lung allocation score era. Marginal donor criteria included age ≥ 55 years old, gender mismatch, ischemic time > 6 hours, history of smoking > 20 pack years, abnormal chest X-ray, abnormal bronchoscopy, and arterial pO2 <350 mmHg on 100% FiO2. Kaplan-Meier analysis was used to compare actuarial survival. Cox regression analysis was used to further delineate significant factors impacting survival. ResultsThere were 10,242 patients who underwent lung transplantation during this time period, and 8895 (87.4%) patients received a marginal donor lung. 3-year survival was 65.7% and 66.7%, respectively, for those who received a marginal donor organ and those who did not (p=0.297). When stratified by single and double lung transplantation, survival was worse for patients who underwent marginal double lung transplantation (p=0.013). Cox regression analysis revealed age ≥ 55 years (p=0.034) and ischemic time >6 hours (p=0.026) as significant factors impacting survival for patients who underwent double lung transplantation. Survival curves for double lung recipients are shown in Figure 1. There were 10,242 patients who underwent lung transplantation during this time period, and 8895 (87.4%) patients received a marginal donor lung. 3-year survival was 65.7% and 66.7%, respectively, for those who received a marginal donor organ and those who did not (p=0.297). When stratified by single and double lung transplantation, survival was worse for patients who underwent marginal double lung transplantation (p=0.013). Cox regression analysis revealed age ≥ 55 years (p=0.034) and ischemic time >6 hours (p=0.026) as significant factors impacting survival for patients who underwent double lung transplantation. Survival curves for double lung recipients are shown in Figure 1. ConclusionDouble lung transplant recipients of marginal donor organs have worse 3-year survival when compared with recipients of non-marginal organs, but those poor outcomes appear to be driven by donors with advanced age and longer ischemic times. Double lung transplant recipients of marginal donor organs have worse 3-year survival when compared with recipients of non-marginal organs, but those poor outcomes appear to be driven by donors with advanced age and longer ischemic times.

Percutaneous Mechanical Thrombectomy for Extensive Acute Lower-Extremity Deep Venous Thrombosis in a Patient After Double-Lung Transplantation

Venous thromboembolism, which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), has been estimated to affect 25% of patients after major surgery; however, the literature on venous thromboembolism after thoracic transplantation and optimal approach remains limited. We report the status of a 67-year-old female who developed massive right lower-extremity DVT after double-lung transplantation. Because her surgery had taken place a week before this event, it was decided that pharmaco-thrombolysis was contraindicated due to the high risk of bleeding complications in a fresh double-lung transplant recipient. The patient was taken emergently to the operating room for percutaneous mechanical thrombectomy, which provided grade III (complete lysis) and restored venous patency in the affected extremity. This report highlights the successful use of purely percutaneous mechanical thrombectomy for acute DVT in a double-lung recipient, and also advocates inferior vena cava filter placement to prevent embolic events during the mechanical thrombectomy.

Inhaled Cyclosporine and Pulmonary Function in Lung Transplant Recipients

Chronic rejection, manifesting as bronchiolitis obliterans, is the leading cause of death in lung transplant recipients. In our previously reported double-blinded, placebo-controlled trial comparing inhaled cyclosporine (ACsA) to aerosol placebo, the rate of bronchiolitis-free survival improved. However, an independent analysis of pulmonary function, a secondary endpoint of the trial, was not performed. We sought to determine the effect of ACsA, in addition to systemic immunosuppression, on pulmonary function. From 1998-2001, 58 patients were randomly assigned to inhale either 300 mg of ACsA (28 patients) or placebo aerosol (30 patients) 3 days a week for the first 2 years after transplantation. Longitudinal changes in pulmonary function of ACsA patients were compared to aerosol placebo patients. In another analysis, the rate of decline from 6-month maximum FEV(1) in randomized patients was compared to the rate of decline in patients receiving conventional immunosuppression from the Novartis transplant database (644 patients, 12 centers worldwide, transplanted from 1990-1995). The average duration of ACsA and aerosol placebo was 400 days +/- 306 and 433 +/- 256, respectively. The change in FEV(1) of ACsA patients (adjusted for Cytomegalovirus (CMV) mismatch and transplant type, followed for a maximum duration of 4.6 years) was superior to the aerosol placebo controls (9.0 +/- 71.4 mL/year vs. -107.9 +/- 55.3, p = 0.007). The FEF(25-75) decreased by -220.3 +/- 117.7 L/(second x year) vs. -412.2 +/- 139.2, p = 0.07, respectively. Similarly, percent FEV(1) decline from maximal values was improved in ACsA patients compared to aerosol placebo and Novartis controls (ACsA -0.43 +/- 1.12%/year vs. aerosol placebo -4.08 +/- 1.4, p = 0.04; ACsA vs. Novartis -4.7 +/- 0.31, p = 0.007). Single-lung recipients receiving ACsA showed improvement in FEV(1) compared to Novartis controls (FEV(1) -0.8 +/- 1.8%/year vs. -4.94 +/- 0.4, p = 0.03) but double-lung recipients showed improvement compared to aerosol placebo controls only (FEV(1) -0.28 +/- 1.22%/year vs. -8.53 +/- 5.95, p = 0.048). In this single center trial, ACsA appears to ameliorate important pulmonary function parameters in lung transplant recipients compared to aerosol placebo and historical control patients. Single- and double-lung transplant recipients may not respond uniformly to treatment, and ongoing randomized trials in lung transplant recipients using ACsA may help elucidate our findings.

Assessment of mean transit time in the engrafted lung with 133Xe lung ventilation scintigraphy improves diagnosis of bronchiolitis obliterans syndrome in living-donor lobar lung transplant recipients

Staging of bronchiolitis obliterans syndrome (BOS) following lung transplantation is based on declines in forced expiratory volume in 1 s (FEV(1)). The aim of this study was to evaluate the usefulness of (133)Xe ventilation scintigraphy in the early detection of BOS following living-donor lobar lung transplantation (LDLLT), to compare (133)Xe washout imaging with computed tomography (CT) findings for early detection of BOS following LDLLT, and to evaluate (133)Xe washout imaging by quantitative analyses. Subjects comprised 30 double-lung recipients and 1 single-lung recipient, who had undergone LDLLT at our institution and survived more than 1 year. Clinically diagnosed BOS developed in six recipients. Declines in graft function were evaluated using a combination of three methods, namely, dynamic spirometry, high-resolution CT (HRCT), and (133)Xe ventilation scintigraphy. Findings for all transplanted lungs were compared between CT and (133)Xe washout imaging. (133)Xe washout imaging was assessed using mean transit time (MTT) of bi-and unilateral lungs. Correlations between MTT of bilateral lungs and FEV(1)% were evaluated. Differences in MTT between BOS and non-BOS lungs, and between non-BOS and donor lungs were also evaluated on unilateral lungs. Appropriate cut-off values of MTT of unilateral lungs were set for the diagnosis of BOS. In all six BOS cases, prolonged-washout images of engrafted lungs revealed early-phase BOS with declines from baseline FEV(1), whereas only one BOS case could be detected using early CT findings of BO (bronchodilatation, decrease in number and size of pulmonary vessels, thickening of septal lines, and volume reduction). A significant correlation was identified between MTT and FEV(1)% (r = -0.346, P < 0.0001). MTT of unilateral lungs was significantly longer in BOS lungs than in non-BOS lungs (P < 0.0001). The cut-off MTT of unilateral lungs for the diagnosis of BOS was set at 64.77 s. Our data show that (133)Xe washout imaging offers excellent potential for early detection of BOS compared with early CT findings. Using (133)Xe washout imaging and MTT with radioactive tracer offers a noninvasive indication of selective ventilatory function in engrafted lungs following LDLLT. MTT appears useful for identifying BOS following LDLLT and allows quantitative evaluation of graft function in unilateral lungs.

Surgical patient outcomes after the increased use of bilateral lung transplantation

Despite the potential limitation of organ availability, several surgical groups have advocated preferential bilateral lung transplantation because of its demonstrated long-term survival advantage. Comparative results for single and sequential double lung transplantation performed at a single center are evaluated to determine whether such a policy improves patient outcome. A retrospective analysis of demographic and outcome data for patients undergoing lung transplantation was performed. Patients were grouped as single or double lung recipients and segregated into diagnostic categories according to the lung allocation scoring system. Era terciles were chosen on the basis of year of transplant, operating surgeon, and transplant volume. Between November 1990 and September 2005, 344 lung transplant procedures were performed in 339 patients. Over three time periods evaluated, the proportion of patients undergoing double lung transplant procedures increased. Overall survivals at 3 months and 1, 3, and 5 years were 89%, 79%, 60%, and 52%, respectively. After adjusting for lung recipient characteristics, survival after double lung transplantation was improved when compared with single lung transplantation (P = .020). Overall patient survival among the three time periods was not significantly different at 30 days and 1 and 3 years despite increasing maximal donor organ ischemia times. In this single-center study, despite longer median allograft ischemic times, as well as greater patient acuity as determined by listing diagnosis, overall early and midterm patient survival has remained higher than nationally reported figures. Bilateral lung transplantation in eligible patients is the procedure of choice.