Current donor selection strategy may be severely limiting the wider application of lung transplantation. Although most series that explore the results of donor selection practice have been limited to single centres and, therefore, necessarily limited in size, reports from some larger institutions have shown that the current level of organ utilization in most of Europe and the United States falls far short of what can be achieved safely [1•]. The more widespread realization of a donor lung utilization rate of in excess of 50% would represent a doubling of current activity in many instances. The perceived risk of early graft failure, although related to certain donor variables in most series, is almost certainly overestimated routinely, which leads to the nonutilization of potentially suitable lungs. Intuitively, the physiology of the donor and the injury induced by brain-stem death must impose some limitations on the tolerance to subsequent ischaemia-reperfusion injury. Selection criteria defined during the early era of lung transplantation with the intention of selecting donors with lungs resistant to this injury have been necessarily strict . Traditional lung transplant donor selection criteria are as follows:
- age ≤ 55 years;
- ABO compatibility;
- clear chest radiograph;
- paO2 ≥ 300 on fiO2 = 1.0, 5 cm H2O positive end-expiratory pressure (PEEP);
- tobacco history ≤ 20 pack years;
- absence of chest trauma;
- no evidence of aspiration/sepsis;
- no prior cardiopulmonary surgery;
- sputum Gram stain – absence of organisms;
- absence of purulent secretions at bronchoscopy.
Many centres have since documented a gradual relaxation of these criteria in an attempt to meet the burgeoning demand for donor lungs. Some limits to donor acceptability have however begun to emerge and as average donor age and comorbidity have increased, the interplay between donor diseases is becoming more important. While the wider application of ex-vivo assessment techniques are awaited, the maximal use of the available donor pool through accurate selection remains the only currently feasible method of optimizing donor utilization.
The mean age of cadaveric organ donors has increased by nearly 5 years since the early days of lung transplantation . By necessity, most centres now routinely accept donors older than the original cut-off of 55 years. Although several reports have shown identical early outcomes with these donors [4,5••], others have found an increased early incidence of early graft dysfunction, even when a relatively conservative age cut-off of 45 years is used . Concerns about reduced graft longevity have also been raised, with older donors (up to 77 years of age) showing a higher incidence of bronchiolitis obliterans syndrome [5••]. Advanced age has been shown to have a detrimental impact on organ function in cardiac , renal  and hepatic  transplantation, and, in biological terms, the lungs of older donors have been shown to produce lower levels of anti-inflammatory interleukin-10 . This finding has been shown to correlate in turn with primary graft dysfunction and may be a plausible biological mechanism for the reduced resilience of older donor lungs to the effects of ischaemia-reperfusion injury. In contrast to earlier reports from the International Society for Heart and Lung Transplantation registry, recent cohorts demonstrate only a modest detrimental effect on survival at 1 and 5 years in recipients receiving lungs from older donors, which does not reach statistical significance . It has been shown previously, however, that donor age interacts with other donor variables to predict poorer outcome. For instance, a prolonged ischaemic time has been shown to have a detrimental impact in transplantation of lungs from older donors . At present, many units will accept the lungs from a donor in their 70s as long as there are no other adverse features, and, in the case of a young donor, will accept prolonged ischaemic times and poorer gas exchange, expecting the greater physiological reserve to allow recovery from ischaemia-reperfusion injury.
Although gas exchange is widely used as the sole objective assessment measure of donor lung function, its shortcomings are manifold. The injurious effects of brain-stem death on pulmonary capillary permeability result in the accumulation of fluid in the lung interstitium  and trigger inflammatory pathways reducing the efficiency of gas exchange in the lung . It is clear that the majority of these changes are reversible , either by aggressive donor management through diuresis, steroids and alveolar recruitment manoeuvres in the short term or in the recipient after transplantation . Unfortunately, it is clear from the increases seen in transplanted lungs with standardized and aggressive donor management algorithms that many lungs are still declined based on an initial poor gas exchange. The traditional acceptable limit of an arterial pO2 of 300 mmHg on an fiO2 of 100% and 5 cmH2O of PEEP has also been shown to be unnecessarily strict, with several studies documenting a gradual relaxation of this guideline (Fig. 1) [14,16–23]. An arterial pO2 lower than this level at the time of donor offer should prompt early assessment of the donor and optimization of haemodynamic status and ventilation, diuresis and appropriate bronchoscopic clearance of any retained secretions, rather than exclusion of the organ donor from lung donation. It is also probably no longer appropriate to consider donors with a low referral arterial pO2 as an extended criteria donor, when oxygenation improves after donor management, as it is clear that outcomes with these donors are equivalent to those with an arterial pO2 greater than 250 mmHg from the outset. Clearly, there are limits to what can be considered an acceptable arterial pO2, and the alarmingly frequent finding (>30%) of thromboembolism in the lungs of declined donors , and even in those accepted for transplantation [25•], remind us that as increasingly low pO2s are accepted, a greater number of donor lungs have abnormalities that may result in severe primary graft dysfunction or not recover at all. Higher risks of early dysfunction, prolonged ventilation and increased early mortality have to be weighed against waiting list mortality, with the knowledge that many causes of poor gas exchange in the donor can be reversed in the recipient if the lungs can be supported through the phase of early dysfunction. A further important limitation of the measurement of arterial pO2 is its inability to distinguish global from unilateral lung dysfunction . The technique of pulmonary vein gas sampling is simple and effective at increasing donor use through identification of good single lungs for transplantation . We have also found this method to predict primary graft dysfunction more reliable and advocate its routine use after donor optimization to aid decision making .
In the current era, few centres would any longer consider smoking to be an exclusion criterion for the lung donor. The traditional recommendation of excluding those with a pack year history in excess of 20 years aimed to eliminate those with chronic damage and resultant poorer graft longevity, but, clearly, current heavy smoking can have a significant detrimental effect on posttransplant outcome also. As in general thoracic surgery , both cumulative smoking history and current intensity have been shown to correlate with posttransplant outcome . Although early gas exchange has been shown to be poorer and duration of ventilation and ICU stay prolonged, there has not been an increase in postoperative mortality with the transplantation of lungs from heavy smokers [30,31]. Importantly, intermediate-term survival and the incidence of bronchiolitis obliterans syndrome have also been comparable. We, therefore, feel that a sole finding of smoking should not be a reason to exclude a potential lung donor.
A ‘clear chest radiograph’ is an uncommon finding in the lung donor as bilateral airspace shadowing due to neurogenic pulmonary oedema and basal volume loss due to atelectasis are common consequences of brain-stem death and prolonged mechanical ventilation . As these abnormalities are largely correctable by appropriate donor management, they should rarely be a cause for exclusion of a potential lung donor . Up to half of those with signs of neurogenic pulmonary oedema on the initial chest radiograph can be expected to show complete resolution by the time of procurement , and even severe oedema has been shown to resolve after transplantation (despite severe primary graft dysfunction). The interpretation of radiographs from the lung donor remains subject to interobserver variability but has been shown to play little role in the ultimate decision whether to use the lungs for transplantation or not . The role of chest radiography should, therefore, be in identifying reversible abnormalities to guide donor management and to identify unilateral abnormality, which, supplemented by pulmonary vein blood gas analysis, can be used to select suitable single lungs for transplantation.
Bronchoscopic abnormality/Gram stain
Apart from the use of bronchoscopy as a therapeutic tool in removing retained airway secretions and allowing judicious broncho-alveolar lavage, normal bronchoscopic appearance has also traditionally formed one of the standard donor selection criteria. Evidence of aspiration of gastric contents, frank inflammation and grossly purulent secretions reaccumulating from the distal airways after suction remain exclusion criteria, but many lesser findings frequently form the basis for nonacceptance of the donor lung. These appearances are subjective and commonplace even in the donor with a normal chest radiograph and gas exchange. Subgroup analysis in small numbers of donors with purulent secretions at bronchoscopy has demonstrated an increased risk of early mortality, but the diagnosis of infection at the time of lung donor assessment remains difficult. Gram stain of tracheal secretions correlates poorly with outcome , and, although culture of broncho-alveolar lavage fluid remains the gold standard for diagnosis of infection in this setting , these results will rarely be available at the time of donor assessment. Donor infection is a common retrospective finding, and transmission to the recipient occurs in up to 8% despite appropriate antibiotic cover . As expected, confirmed infection predicts prolonged ventilation and intensive care unit stay, but the presence of organisms in the donor has been shown to correlate poorly with the development of posttransplantation pneumonia in the recipient . We would, therefore, consider most secretions acceptable, provided there is no reaccumulation from the distal airways following thorough bronchial toilet.
The prolongation of allograft ischaemic time has the potential to increase activity in large procurement regions, allowing greater geographical sharing of organs and possibly enabling improved donor–recipient matching. Early International Society for Heart and Lung Transplantation (ISHLT) registry analyses and institutional reports  showed a distinct early survival disadvantage with ischaemic times in excess of 6 h, and a large multicentre report confirmed poorer early graft function beyond an ischaemic time of 330 min and a hazard ratio for death at 1 year of 2.70 [95% confidence interval (CI) 1.93–3.78] . Most of these studies largely predated current preservation strategy. The theoretical possibility exists that current methods may increase tolerable ischaemic times. It would appear that the lung transplant community has accepted this finding as the case as the ISHLT registry data for the period 2003–2006 shows 24% of reported ischaemic times exceeding 6 h and 5% exceeding 8 h. Questions remain regarding a possible higher rate of early graft dysfunction and decreased graft longevity. A further important consideration is the finding in earlier series of an interaction between donor age and ischaemic time . In current practice, longer ischaemic times in excess of 8 h will, therefore, be accepted only in the young, otherwise healthy donor.
It is, therefore, becoming clear that individual unmet standard donor criteria are rarely sufficient to prompt nonacceptance of the potential lung donor. Instead, the interaction of factors should be considered, each on a continuum from ideal to highly predictive of adverse outcome. Although we await more sensitive objective predictors of donor lung function and posttransplant outcome, good judgement and experience in donor selection remain the cornerstones of donor selection. The development of a donor scoring system to calculate a predicted risk would greatly improve decision making and allow between-centre comparison of outcomes. This development has been proven feasible on a single centre scale [41•], but wider application will require concerted collection of donor demographics and outcomes including primary graft dysfunction scores. Increasingly, the matching of the extended criteria donor to specific recipient groups will also become an issue. Each potential recipient would like to receive a perfect allograft, and the transplant centre would prefer to only use such organs, but clearly, with growing waiting lists and increasing waiting list mortality, this option is not a possibility. The use of lungs of truly marginal quality may only be justified in recipients falling out with standard recipient selection criteria. These will necessarily be high-risk transplants with generally poorer outcomes .
At present, there are no scientific answers to many questions regarding donor acceptability in individual circumstances, and, as such, donor selection and matching with a suitable recipient remain an art. The available evidence does however support the premise that the precious resource of the cadaveric lung donor continues to be widely underutilized. Improvements in this situation will require the continued study of outcomes with the use of extended criteria lung donors in a concerted multicentre effort.
There was no conflict of interests.
References and recommended reading
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