Ex vivo lung perfusion in donation after circulatory death: A post hoc analysis of the Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donors Lungs trial.

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

Geographic disparities in lung transplantation in the United States before and after the November 2017 allocation change.

BACKGROUND: The primary lung allocation unit was expanded from the donation service area to a 250-mile radius in 2017. Prior to the change, geographic disparities in donor lung availability impacted waitlist outcomes. We sought to determine if the new allocation system improved these disparities. METHODS: We conducted a retrospective cohort study comparing the 2-year period before and after the change. Donor lung availability was defined as the ratio of donor lungs to waitlist candidates in the primary allocation unit. Transplant centers were divided into quartiles by donor lung availability. Multivariable competing risk models were used to determine the association between lung availability and waitlist outcomes. Multivariable Cox proportional hazards models compared post-transplant survival. RESULTS: Prior to the allocation change, the unadjusted transplant rate at centers in the lowest and highest quartiles was 132 and 607 transplants per 100 waitlist years. Candidates in the lowest quartile of donor lung availability had a 61% adjusted lower transplantation rate compared to candidates in highest quartile (sub-hazard ratio [sHR]: 0.39, 95% confidence interval [CI]: 0.34-0.44). After the allocation change, the disparity decreased resulting in an unadjusted transplant rate of 141 and 309 among centers in the lowest and highest quartiles. Candidates in the lowest quartile had a 38% adjusted lower transplantation rate compared to those in the highest (sHR: 0.62, 95% CI: 0.57-0.68). There was no significant difference in 1-year post-transplant survival. CONCLUSIONS: Although the expansion of the primary allocation unit improved disparities in waitlist outcomes without any change in post-transplant survival, there still remain significant differences due to geography.

Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study.

Despite the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation, with the majority of donor lungs being allocated locally to lower-priority candidates. We conducted a retrospective cohort study of 19 622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (subdistribution hazard ratio [SHR]: 1.84, 95% confidence interval [CI]: 1.51-2.24, P < .001). The transplantation rate was 57% lower in the lowest quartile compared with the highest (SHR: 0.43, 95% CI: 0.39-0.47). The adjusted death or removal rate decreased by 11% with a 50% increase in local lung availability (SHR: 0.89, 95% CI: 0.85-0.93, P < .001) and the adjusted transplantation rate increased by 19% (SHR: 1.19, 95% CI: 1.17-1.22, P < .001). There are geographically disparate waitlist outcomes in the current lung allocation system. Candidates listed in areas of low local lung availability have worse waitlist outcomes.

Refining Low Physical Activity Measurement Improves Frailty Assessment in Advanced Lung Disease and Survivors of Critical Illness.

RATIONALE: The frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients. OBJECTIVES: To test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument. METHODS: In separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors. RESULTS: Among 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP-DASI HR, 2.99; 95% CI, 1.03-8.65) and with mortality in older ICU survivors (FFP-MLTA HR, 2.68; 95% CI, 0.62-11.6; FFP-DASI HR, 5.71; 95% CI, 1.34-24.3). CONCLUSIONS: The DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.

Donor lung assessment using selective pulmonary vein gases.

OBJECTIVES: Standard donor lung assessment relies on imaging, challenge gases and subjective interpretation of bronchoscopic findings, palpation and visual assessment. Central gases may not accurately represent true quality of the lungs. We report our experience using selective pulmonary vein gases to corroborate the subjective judgement. METHODS: Starting, January 2012, donor lungs have been assessed by intraoperative bronchoscopy, palpation and visual judgement of lung collapse upon temporary disconnection from ventilator, central gases from the aorta and selective pulmonary vein gases. Partial pressure of oxygen (pO2) <300 mmHg on FiO2 of 1.0 was considered low. The results of the chest X-ray and last pO2 in the intensive care unit were also collected. Post-transplant primary graft dysfunction and survival were monitored. RESULTS: To date, 259 consecutive brain-dead donors have been assessed and 157 transplants performed. Last pO2 in the intensive care unit was poorly correlated with intraoperative central pO2 (Spearman's rank correlation rs = 0.29). Right inferior pulmonary vein pO2 was associated (Mann-Whitney, P < 0.001) with findings at bronchoscopy [clean: median pO2 443 mmHg (25th-75th percentile range 349-512) and purulent: 264 mmHg (178-408)]; palpation [good: 463 mmHg (401-517) and poor: 264 mmHg (158-434)] and visual assessment of lung collapse [good lung collapse: 429 mmHg (320-501) and poor lung collapse: 205 mmHg (118-348)]. Left inferior pulmonary pO2 was associated (P < 0.001) with findings at bronchoscopy [clean: 419 mmHg (371-504) and purulent: 254 mmHg (206-367)]; palpation [good: 444 mmHg (400-517) and poor 282 mmHg (211-419)] and visual assessment of lung collapse [good: 420 mmHg (349-496) and poor: 246 mmHg (129-330)]. At 72 h, pulmonary graft dysfunction 2 was in 21/157 (13%) and pulmonary graft dysfunction 3 in 17/157 (11%). Ninety-day and 1-year mortalities were 6/157 (4%) and 13/157 (8%), respectively. CONCLUSIONS: Selective pulmonary vein gases provide corroborative objective support to the findings at bronchoscopy, palpation and visual assessment. Central gases do not always reflect true function of the lungs, having high false-positive rate towards the individual lower lobe gas exchange. Objective measures of donor lung function may optimize donor surgeon assessment, allowing for low pulmonary graft dysfunction rates and low 90-day and 1-year mortality.

Short Stature and Access to Lung Transplantation in the United States. A Cohort Study.

RATIONALE: Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates. OBJECTIVES: To examine the relationship between lung transplant candidate height and waiting list outcomes. METHODS: We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year. MEASUREMENTS AND MAIN RESULTS: The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170-176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval [CI], 29-39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24-96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10-85%) higher rate of respiratory failure while awaiting lung transplantation. CONCLUSIONS: Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height.

Modified Transverse Thoracosternotomy and Cost-Effective Reinforced Sternal Closure.

The bilateral transverse thoracosternotomy clamshell incision provides excellent exposure to the mediastinal structures in double lung transplantation. The use of a modified transverse sternotomy and a figure of 8 configuration with one monofilament metal wire, along with two longitudinal wires across the sternal division, results in greater stability and equally distributed oblique tension. Our described technique was more cost effective and resulted in no incidence of dehiscence. We present our experience using a modified transverse sternotomy and reinforced sternal closure method.

High lung allocation score is associated with increased morbidity and mortality following transplantation.

BACKGROUND: The lung allocation score (LAS) was initiated in May 2005 to allocate lungs based on medical urgency and posttransplant survival. The purpose of this study was to determine if there is an association between an elevated LAS at the time of transplantation and increased postoperative morbidity and mortality. METHODS: The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant recipients aged >or= 12 years who received transplants between April 5, 2006, and December 31, 2007 (n = 3,836). Recipients were stratified into three groups: LAS < 50 (n = 3,161, 83.87%), LAS 50 to 75 (n = 411, 10.9%), and LAS >or= 75 (n = 197, 5.23%), referred to as low LAS (LLAS), intermediate LAS (ILAS), and high LAS (HLAS), respectively. The primary outcome was posttransplant graft survival at 1 year. Secondary outcomes included length of stay and in-hospital complications. RESULTS: HLAS recipients had significantly worse actuarial survival at 90 days and 1 year compared with LLAS recipients. When transplant recipients were stratified by disease etiology, a trend of decreased survival with elevated LAS was observed across all major causes of lung transplant. HLAS recipients were more likely to require dialysis or to have infections compared with LLAS recipients (P < .001). In addition, length of stay was higher in the HLAS group when compared with the LLAS group (P < .001). CONCLUSIONS: HLAS is associated with decreased survival and increased complications during the transplant hospitalization. Whereas the LAS has improved organ allocation through decreased waiting list deaths and waiting list times, lower survival and higher morbidity among HLAS recipients suggests that continued review of LAS scoring is needed to ensure optimal long-term transplant survival.

Assessment of kidney function in lung transplant candidates.

BACKGROUND: Glomerular filtration rate (GFR) is the best measure of kidney function; however, 24-hour creatinine clearance (CrCl) is the initial screening test used for lung transplant candidates at most centers. Although creatinine-based formulas that estimate GFR have been derived, none have been validated in patients with severe lung disease. METHODS: We performed a retrospective cohort study of patients evaluated for lung transplantation at Columbia Presbyterian Medical Center and compared the GFR estimated from the Modification of Diet in Renal Disease (MDRD) and other formulas to the CrCl. We then validated these results in a cohort of patients evaluated at the Hospital of the University of Pennsylvania. RESULTS: There were strong and statistically significant direct correlations between estimated GFR and CrCl. An estimated GFR of <95 ml/min by the MDRD was very sensitive at detecting kidney dysfunction by CrCl in the derivation cohort. In the validation cohort, the negative predictive value of this cut-off was 97%. CONCLUSIONS: Established formulas for estimating GFR are highly discriminating for kidney dysfunction in patients being evaluated for lung transplantation and may actually have greater validity than CrCl in some instances.