Methods
Study Population
All LTx candidates registered in Germany between December 10, 2010 and December 9, 2011 (pre-LAS period) as well as those registered between December 10, 2011 and December 9, 2012 (post-LAS period) were included. Additionally, all transplants performed in this 2-year study period were included and followed up until March 9, 2013, providing complete 3-month follow-up after transplantation.
Diagnosis Classification
All patients were classified according to underlying disease into the following categories: chronic obstructive pulmonary disease (COPD; emphysema and alpha 1 antitrypsin deficiency); idiopathic pulmonary fibrosis (IPF; all undetermined forms of pulmonary fibrosis, all idiopathic interstitial pneumonia [nonspecific, desquamative interstitial, cryptogenic organizing pneumonia], hypersensitivity pneumonitis); cystic fibrosis (CF; excluding re-listing); pulmonary hypertension (PH; including idiopathic PH, pulmonary veno-occlusive disease, Eisenmenger's syndrome); other (all re-listings, pulmonary fibrosis with connective tissue diseases [rheumatoid arthritis, scleroderma], histiocytosis X, lymphangioleiomyomatosis, alveolar proteinosis, bronchiectasis, sarcoidosis, graft-versus-host disease).
Lung Allocation Policy Changes
Prior to implementation of the LAS on December 10, 2011, all donor lungs were allocated according to an urgency tier system, based on both urgency and waiting time. Patients were classified as elective (T), urgent (U) or high urgent (HU), with those in the latter two categories being mandatorily hospitalized and considered too ill for discharge before transplantation. HU patients must be admitted to the intensive care unit in addition. Actual assignment of the HU and U status was performed by a team of three independent transplant experts, who decide by majority vote, with guidance by disease-specific criteria, whether a patient can be upgraded to HU and U. Patients with HU status were prioritized over U and T patients; and within the same urgency tier, patients waiting longest received the lung offer first.
In October 2010, the German Organ Commission of the German Medical Council decided to introduce the LAS system in Germany; more specific, the same LAS model used in the United States was implemented. From December 10, 2011, all candidates listed for LTx were transferred to the LAS system. Patients were thereafter considered to be either electively transplantable (T) or nontransplantable (NT), with both U and HU statuses being abandoned. Germany is a member of Eurotransplant (ET), where trans-border exchange of organs between member countries is possible for eligible international HU patients or in cases where no national recipient is available. In ET, long-standing rules regarding international exchange have been established. Following introduction of LAS in Germany, international urgency was harmonized by defining—for arbitrary reasons—a "high LAS" group of 50 or higher. Transplant programs in the non-LAS member countries of ET submitted LAS data only for HU patients to qualify for trans-border exchange.
Allocation to Pediatric Transplant Candidates
All LTx candidates under the age of 12 years listed in Germany automatically receive an LAS value of 100 and are thereafter sorted by waiting time. Similar to the US organs from adolescent donors (12–18 years) were prioritized to adolescent recipients before being offered to pediatric recipients in an attempt to promote transplant probability in this age group. But in contrast to the United States, all patients are on one single-transplant waiting list and there is broad geographical sharing for all patients with an LAS above 50; including pediatric transplant candidates. In addition, there are no candidate age categories in case of adult lung donors; this implies that all transplant candidates, irrespective of their age, are sorted by LAS; hence, children may receive offers from suitable adult lung donors, provided that a size reduced or lobar transplantation is feasible.
LAS Exceptions
The LAS is a calculated value designed to reflect disease severity and predict outcomes after transplantation. In some patients, however, the calculated LAS may not accurately reflect urgency/outcome and therefore the option to submit an exceptional LAS (eLAS) was introduced.
A defined policy on the indications and assignment of eLAS—analog to the US LAS—was established, referring principally to patients with PH class 1, 1' and 4, combined nonrenal transplants and rare diseases not included in the LAS diagnosis list. In addition, eLAS requests may be submitted for any patient where the calculated LAS is not felt to adequately reflect the urgency and expected outcome. Business rules were developed for data entry on mechanical ventilation and extracorporeal support without intubation to adjust for "pseudo-normalization" of blood gas parameters and oxygen demand in patients receiving extracorporeal support.
Rescue Versus Standard Allocation
In cases where a donor lung has been declined due to donor-related medical grounds on at least three occasions or risk of imminent organ loss due to unstable donor condition exists, allocation may be switched to "rescue allocation." This additional scheme aims to maximize organ placement and differs from standard allocation in that offers are no longer made to individual patients, rather to participating transplant centers, who may then select any listed local candidate irrespective of LAS value, urgency status or waiting time.
Statistics
Donor, recipient and transplant factors are displayed either as total number and percentage or as median and interquartile ranges. Categorical variables were analyzed with a chi-squared test and continuous variables with a Mann–Whitney U-test. All analyses were performed with SPSS version 20.0 (IBM Corporation, Armonk, NY). Survival rates after waiting list registration were analyzed using competing risk methods; survival rates after LTx were estimated using Kaplan–Meier estimation and Cox-regression models. For all analyses, a p-value of <0.05 was considered significant.