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BACKGROUND: Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to less than 200 days and decreasing mortality on the waitlist. A current challenge is the wait for the waitlist—the time between patient’s transplant-eligible diagnosis and waitlist registration. METHODS: We investigated whether sociodemographic (age, sex, race, insurance, marital status, median household income) and clinical (FEV(1) % of predicted, body mass index, depression/anxiety, alcohol/substance misuse, absolute/relative contraindications) factors influenced referral and waitlist registration. We conducted a retrospective cohort study through chart review of hospitalized patients on the University of Chicago general medicine service from 2006–2014 meeting transplant-eligible criteria and ICD-9 billing codes for cystic fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant-eligibility to referral, work-up, and waitlist using Kaplan-Meier curves and log-rank tests. RESULTS: Overall, referral rates for transplant-eligible patients were 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs. PF 22%, p

Background Although postoperative predicted forced expiratory volume in the first second and diffusing capacity of lung (ppoFEV 1 % and ppoDLCO%, respectively) have been identified as independent predictors of postoperative pulmonary complications after open lobectomy, it has been suggested that their predictive abilities may not extend to patients undergoing minimally invasive lobectomy. Methods We evaluated outcomes in 805 patients undergoing isolated lobectomy through open (n = 585) or minimally invasive approaches (n = 220) using a prospective database. Demographic and physiologic data were extracted and compared with complications classified as pulmonary, cardiac, other, mortality, and any. Results Patients included 428 women and 377 men; mean age was 65.0 years. Minimally invasive patients were older (66.6 versus 64.3 years, p = 0.006), had better ppoFEV 1 % (71.5% versus 65.6%, p p = 0.017), and less often underwent induction therapy (0.5% versus 4.8%, p = 0.003). Pulmonary and other complications were less common after minimally invasive lobectomy (3.6% versus 10.4%, p = 0.0034; 8.6% versus 15.8%, p = 0.008). Operative mortality occurred in 1.4% of minimally invasive patients and 3.9% of open patients ( p = 0.075). Pulmonary complication incidence was related to predicted postoperative lung function for both minimally invasive and open approaches. On multivariate analysis with stratification for stage, ppoFEV 1 % and ppoDLCO% were predictive of pulmonary complications for both minimally invasive and open approaches. Conclusions Our results suggest that the predictive abilities of ppoFEV 1 % and ppoDLCO% are retained for minimally invasive lobectomy and can be used to estimate the risk of pulmonary complications.

The purpose of this contribution is to review the development and scope of postgraduate training and educational affairs of the International Society of Heart and Lung Transplantation.

Background It has been previously shown that donor treatment with aprotinin or inhaled nitric oxide reduces reperfusion injury after lung transplantation in animals. These studies used living donors with normal lungs. However, the main source of lungs for transplantation is brain-dead donors. Brain death causes systemic inflammatory response and lung injury, rendering the organ susceptible to reperfusion injury after transplantation. We hypothesized that treatment with aprotinin or inhaled nitric oxide after brain death would improve the donor inflammatory response and reduce lung reperfusion injury after transplantation. Methods Brain death was induced in 24 rats by intracranial balloon inflation. Subsequently, the animals received intravenous aprotinin ( n = 8), inhaled nitric oxide ( n = 7), or no treatment ( n = 9) for 5 hours. The lungs were retrieved and reperfused for 2 hours using recipient rats. Results After brain death, oxygenation deteriorated earlier and significantly more in rats that received treatment, especially with nitric oxide. Treatment did not reduce the donor systemic inflammatory response as assessed by serum levels of proinflammatory cytokines. Oxygenation, airway pressure, pulmonary vascular resistance, lung water index and bronchoalveolar lavage cytokine levels were similar after reperfusion of grafts from all three groups of donors. Conclusions Donor treatment with aprotinin or inhaled nitric oxide does not improve lungs that have been injured by brain death.

Sympathetic discharge and hypertensive crisis often accompany brain death, causing neurogenic pulmonary edema. Progressive systemic inflammatory response develops, which can injure the lung further. We investigated whether (a) early hemodynamic injury during donor brain death increases reperfusion injury after lung transplantation and (b) delaying lung recovery would augment reperfusion injury further, because of the progressive systemic inflammatory response in the donor. Brain death was induced by intracranial balloon inflation in rats, with or without alpha-adrenergic blockade pretreatment to prevent the hypertensive crisis. Another group of rats had a sham procedure. Lungs were retrieved 15 min after brain death or sham procedure and reperfused using recipient rats. In a fourth group, brain death was induced and the lungs were retrieved 5 h after brain death and reperfused. Postreperfusion, lungs retrieved early from untreated brain-dead donors developed more severe reperfusion injury, as assessed by functional parameters and inflammatory markers, than those from sham or alpha-blockade-treated donors. Lungs retrieved late from brain-dead donors had similar inflammatory markers after reperfusion to those retrieved early, but significantly lower pulmonary vascular resistance. Early hemodynamic damage during donor brain death increases reperfusion injury after lung transplantation. Delaying retrieval may allow the lung to recover from the hemodynamic injury.

Brain-dead donors are the major source of lungs for transplantation. Brain death is characterized by two hemodynamic phases. Initially, massive sympathetic discharge results in a hypertensive crisis. This is followed by neurogenic hypotension. Up-regulation of pro-inflammatory mediators occurs in all organs and lung injury develops; this can adversely affect graft function post-transplantation. The mechanisms of the systemic and lung inflammation are unknown. We hypothesized that the hemodynamic changes are responsible for these inflammatory phenomena. Brain death was induced by intra-cranial balloon inflation in rats. This resulted in hypertensive crisis, followed by hypotension. There was a significant increase in blood neutrophil CD11b/CD18 expression and pro-inflammatory cytokine levels in serum and bronchoalveolar lavage, compared with control animals. Rupture of the capillary-alveolar membrane was demonstrated by electron microscopy. Elimination of the hypertensive response by alpha-adrenergic antagonist pre-treatment prevented inflammatory lung injury, reduced the systemic inflammatory markers and preserved capillary-alveolar membrane integrity. Correction of the neurogenic hypotension with noradrenaline ameliorated the systemic inflammatory response and improved oxygenation. We conclude that the sympathetic discharge triggers systemic and lung inflammation, which can be further enhanced by neurogenic hypotension. Management of the brain-dead donor with early anti-inflammatory treatment and vasoconstrictors is warranted.

Mitral valve dysfunction after orthotopic heart transplantation may cause symptoms refractory to medical therapy. In this report, we present a patient who underwent mitral annuloplasty for severe symptomatic mitral valve insufficiency 9 years after heart transplantation, and we critically appraise the literature available for mitral valve dysfunction in this setting. Mitral valve repair, when feasible, should be considered for mitral insufficiency after transplantation to improve functional status and reduce the risk of retransplantation--this is particularly prudent in view of chronic donor shortage.

Purpose: SLTx is advocated to optimize organ availability for endstage obstructive or fibrotic respiratory disease.Contra-lateral native lung hyperinflation in recipients with obstructive lung disease may limit functional improvements after SLTx. We hypothesized that recipients with fibrotic lung disease will achieve higher best FEV1 after SLTx than obstructive recipients. Methods and Materials: Single centre, retrospective review of recipients surviving more than 12 months after SLTx for fibrotic or obstructive disease was performed. Pre-transplant spirometry, total lung capacity (TLC) and residual volume (RV) were correlated with the best achieved FEV1 after SLTx. The best post-transplant FEV1 was compared between the fibrotic and obstructive recipients. Results: 57 SLTx recipients were included, 35 obstructive, median age 55yrs (range 37-64), 22 fibrotic, 57yrs (30-64). Post-SLTx survival was not different between the two groups 7.4 v 6.5 yrs respectively. Pre-transplant lung function showed significantly higher TLC (7.99 v 3.50 l, p 0.001Mann-WhitneyU test), RV (5.91 v 1.36 l, p 0.001) and lower FEV1 (0.66 v 1.59 l/s, p 0.001) in obstructive recipients compared with fibrotics. Post-SLTx, the maximal achieved FEV1 was significantly higher in fibrotics (2.38 v 1.83 l/s, p 0.0004). The best post-SLTx FEV1 was corrected for sex, height & age as % predicted FEV1 and showed higher values in the fibrotic group (72.8% v 57.3%, p 0.002). There was no correlation between pre-transplant % predicted TLC or RV and post-SLTx % predicted FEV1in obstructive recipients (r 0.11 p 0.6 Spearman). Conclusions: SLTx recipients for fibrotic lung disease achieve better maximal FEV1 than those with obstructive disease. Our data suggest that native lung hyperinflation in patients with obstructive disease may not be the only factor to account for this difference. Single lung transplantation should be the operation of choice in patients with fibrotic lung disease. The lower achieved lung function in obstructive disease is more complex than hyperinflation and requires further investigation.

Purpose: Brain death is accompanied by hypertensive crisis followed by hypotension. We examined the role of the haemodynamic changes in the systemic neutrophil activation and lung injury. Procedures: Rats (n 49) were anaesthetised and ventilated. Brain death was induced by intracranial balloon inflation in 37: a) “BD” group (n 13); b) “Phentolamine” group (n 12) received phentolamine before balloon inflation to prevent hypertension; c) “Noradrenaline” group (n 12) received intravenous infusion of noradrenaline after brain death to correct hypotension. In 12 rats (Sham) a balloon was inserted, but not inflated. Arterial blood gases and blood neutrophil CD11b/CD18 were measured for 4 h. Lungs were examined with transmission electron microscopy (TEM). Results: In BD, balloon inflation increased mean arterial pressure (MAP) to 150 14.5 mmHg (p 0.001). MAP then fell to a hypotensive plateau (p 0.001). In Phentolamine, the drug decreased MAP by 31 6.9%. Subsequent balloon inflation increased MAP, but not higher than Sham levels (p 0.8). MAP then fell to a plateau, similar to BD (p 0.4). In Noradrenaline, plateau MAP was increased to Sham levels (p 0.3). The BD group had significant metabolic acidosis (MA)(p 0.001), increased alveolo-arterial difference in partial oxygen pressure (P[A-a]O2)(p 0.036) and higher neutrophil CD11b/CD18 levels (p 0.01), compared with Sham. In Phentolamine, P[A-a]O2 and CD18 were similar to Sham, but MA was worse (p 0.001) and CD11b was higher (p 0.049). In Noradrenaline, all variables were similar to Sham (p 0.05). TEM revealed areas of full-thickness capillary-alveolar membrane rupture in BD and Noradrenaline. Lungs from Sham and Phentolamine were normal. Conclusions: The hypertensive crisis associated with brain death can cause stress failure of the pulmonary capillaries, neutrophil activation and lung dysfunction in the transplant donor, which are blocked by phentolamine. Further neutrophil activation and lung injury can be induced by neurogenic hypotension and organ ischaemia, and are reversed by noradrenaline. Optimal donor management requires control of both phases.

AMELIORATED REPERFUSION INJURY IN LUNG TRANSPLANTATION AFTER REDUCTION OF BRAIN DEATH INDUCED INFLAMMATORY GRAFT DAMAGE IN THE DONOR C.H. Wigfield, H.D. Golledge, B.K. Shenton, J.A. Kirby, J.H. Dark, Department of Cardiothoracic Surgery and Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom; Comparative Biology Centre, University of Newcastle, Newcastle upon Tyne, United Kingdom; Department of Surgery, University of Newcastle, Newcastle upon Tyne, United Kingdom