INTRODUCTION — Optimal selection and care of donor lungs for transplant are needed to increase the number of successful lung transplantations. Deceased donor evaluation and selection after brain and cardiac death will be reviewed here from the lung transplant perspective.
Lobar lung procurement from living donors is exceedingly rare; living donor eligibility and selection is beyond the scope of this topic. The general approach to potential deceased organ donors including identification of donors, referral to organ procurement organizations (OPO), and the differing responsibilities of the treating providers and the OPO are discussed separately. Management of the deceased organ donor before and during procurement is also covered elsewhere.
●(See "Lung transplantation: Disease-based choice of procedure".)
●(See "Evaluation of the potential deceased organ donor (adult)".)
●(See "Management of the deceased organ donor".)
The indications for lung transplantation, selection of lung transplant recipients, and techniques for lung procurement and preservation are reviewed separately.
●(See "Lung transplantation: An overview".)
●(See "Lung transplantation: General guidelines for recipient selection".)
●(See "Lung transplantation: Donor lung procurement and preservation".)
DONATION AFTER BRAIN DEATH — Most allografts from deceased donors are procured following declaration of death by neurologic criteria (brain death). Donor evaluation begins with the notification of the local organ procurement organization (OPO) of a potential donor. A member of the OPO, or a provider trained in the consent of families for organ donation, should approach the family as soon as reasonable after the determination of brain death [1]. (See "Diagnosis of brain death".)
When the patient has signed an irrevocable consent for transplant (offered through some state registries), the OPO staff will support the family through the organ retrieval and grieving process. If consent has not already been provided by the patient, the OPO staff will explain the procurement process to the family, including the dignity of the process and implications for funeral arrangements, and obtain their consent [2]. The OPO staff will also coordinate evaluation of the donor for suitability for transplant and will communicate with the United Network for Organ Sharing (UNOS) to match the donor with an appropriate recipient from the waiting list. (See "Lung transplantation: An overview".)
DONATION AFTER CIRCULATORY DEATH
Definition and epidemiology — Some experts recommend that the phrase "donation after circulatory determination of death" (DCDD) replace "donation after cardiac death" or "nonbeating heart donation (NHBD)." These experts emphasize that organ donation occurs after cessation of circulatory and respiratory, not cardiac, function [3]. Recently, "controlled donation after circulatory death" (cDCD) or "donation after circulatory death" (DCD) gained more traction in the literature. There is no official consensus on the terminology.
DCD has become an accepted method of increasing the donor pool in some transplant centers and organ procurement organizations (OPOs) [4], although the exact definition of circulatory death and the timing of organ procurement remain controversial. Nonheartbeating donors can be classified according to the Maastricht system, which was developed in 1995 and revised in 2014 [5,6]:
●I Dead on arrival to hospital
●II Unsuccessful resuscitation
●III Awaiting cardiac arrest (inpatient withdrawal of support)
●IV Cardiac arrest while brain-dead
●V Euthanasia/medically assisted cardiocirculatory death
Since the first successful transplantation of lungs from a nonheartbeating donor in 2001, ethical and legal frameworks have been put in place to investigate and utilize increasing numbers of allografts from nonheartbeating donors [7,8]. Up to 20 to 60 percent of all lung transplants come from DCD in Australian and European centers, the majority of which are DCD-III [9]. Small numbers of DCD-V lung transplants have also been permitted in the Netherlands and some provinces of Canada, with equivalent outcomes to DCD-III donation [10-12]. DCD accounts for only a small percentage of deceased organ donors in the United States with the majority of lung transplant programs having never performed such transplantation. According to the Organ Procurement and Transplant Network annual data report, almost 7 percent of lung transplant recipients received lungs from DCD donors in 2020 [13]. The majority of transplants are from donation after brain death, discussed above. (See 'Donation after brain death' above.)
Situations in which DCD may be considered include irreversible brain injury, end stage musculoskeletal disease, and high spinal cord injury [14,15]. These criteria may be used when the donor does not meet criteria for brain death (see 'Donation after brain death' above). Other situations include severe critical illness, sudden death without significant thoracic or abdominal trauma, known time of cardiac arrest, and cardiopulmonary resuscitation maneuvers started within 15 minutes of cardiac arrest [14].
Protocol — The details of protocols and management recommendations for DCD have been the subject of consensus conferences followed by practice guidelines [14,16].
●Decision to withdraw life-sustaining therapies – The decision to withdraw life-sustaining therapies should only be made by the treating clinician/team and patient family members or proxies. It should not be influenced by the prospect of organ donation. Organ transplant professionals have no role and must not be involved in this decision.
●Antemortem evaluation – The local OPO staff should become involved immediately after the decision is made to withdraw life-sustaining treatment. The OPO staff will coordinate communication with the United Network for Organ Sharing (UNOS), the transplant team, and the family during the evaluation of the donor's suitability for transplant. (See "Lung transplantation: An overview".)
Ante mortem interventions are ethically appropriate if they contribute to good transplant outcomes and have a low chance of harming a prospective donor [8]. These may include obtaining blood samples, performance of bronchoscopy, placement of a nasogastric tube to decompress the stomach, injection of heparin to prevent thromboembolism, use of vasodilatory agents to improve organ perfusion, and the placement of arterial and/or venous cannulae for rapid access at the time of death [8].
●Timeframe for withdrawal of life-sustaining therapy – In the setting of withdrawal of life-sustaining treatment, the time limit to circulatory death after treatment withdrawal may be up to two hours and still enable organ recovery. Several studies have developed criteria to help predict the likelihood of circulatory death within 60 to 120 minutes after planned withdrawal of life support, but more research is needed to help optimize timing of withdrawal of life-sustaining treatments and to reliably identify those who will die within two hours after withdrawal, as described separately. (See "Evaluation of the potential deceased organ donor (adult)", section on 'Donation after circulatory determination of death (DCDD)'.)
●Declaration of death – Organ procurement must follow irreversible cessation of life; organ retrieval may not cause the death of the donor.
•Definition of circulatory death – Clinical examination that reveals the absence of responsiveness, heart sounds, pulse, and respiratory effort defines circulatory death. Confirmatory tests may be performed in accordance with the hospital protocol demonstrating any of the following criteria to prove absence of circulation [17,18]:
-Absence of arterial pulsations observed by an indwelling arterial line
-Absence of opening of the aortic valve by echocardiography
-Absence of circulation by arterial Doppler studies
-Absence electrical activity on an electrocardiogram
•Observation period following circulatory death – Most OPO and hospital policies require an observation period of five minutes without circulation to confirm the absence of circulation is permanent [9,16], although some continue to follow older guidelines of two to five minutes [15,19].
•Special considerations for normothermic regional perfusion (NRP) – To assist in organ recovery from warm ischemic insult during controlled DCD, centers are increasingly using abdominal or thoraco-abdominal NRP after the declaration of death [20]. This re-establishment of circulation to the abdomen, heart, and lungs after the declaration of death has raised ethical concerns [21]. Some societies advocate a mandatory five-minute observation period in this setting to rule out autoresuscitation as well as contingency plans to abort NRP if there are any concerns that death criteria are not satisfied [9].
OUTCOMES BASED ON DONATION TYPE — Donation after circulatory death (DCD) and donation after brain death (DBD) have demonstrated similar lung transplantation graft survival in multiple observational cohorts.
●A systematic review and a large international multi-center registry study of lung transplantation outcomes showed no difference in short or long-term survival between DCD and DBD [22,23]. A follow-up multicenter registry study focusing on only the high-risk recipients (patients bridged with extracorporeal membrane oxygenation, patients with idiopathic pulmonary arterial hypertension, and retransplants) also found no difference in long-term survival between DCD and DBD [24].
●In a six-year single-center study that included 60 transplants from DCD donors, there was a higher incidence of primary graft dysfunction grade 3 and higher risk of bronchiolitis obliterans syndrome (BOS) in the long-term follow-up; however, the overall cumulative survival was not significantly different [25].
●A separate study using data from the United Network for Organ Sharing (UNOS) compared graft survival in 479 recipients of lungs from brain-dead donors that had been resuscitated from a cardiac arrest that occurred after declaration of brain death with survival of lung grafts from nonarrest donors [26]. No significant difference was found in perioperative mortality, airway dehiscence, dialysis requirement, postoperative length of stay, or overall survival.
Strategies to maintain the integrity of the allograft and reduce ischemic times from the moment of circulatory death to transplantation are key to the success of DCD. A discussion of potential interventions to preserve lung function is presented separately. (See "Lung transplantation: Donor lung procurement and preservation".)
DONOR SELECTION — No controlled data exist to determine what constitutes ideal donor candidacy. Consensus and experience have identified some ideal and other less than ideal, or "expanded," donor characteristics that are reviewed here.
Since the lung donor usually will be donating other organs, coordination between transplant teams is critical to allow recovery of multiple organs at nearly the same time. Further information regarding donor organ preservation is presented separately. (See "Lung transplantation: Donor lung procurement and preservation".)
Size matching — Matching of the size of a donor lung with a recipient is usually based on donor and recipient height, although some centers also use estimates of lung volume made from chest radiographs [27,28]. While the optimal degree of fit is unknown and the correlation between donor and recipient size need not be perfect, a close size match is preferred [29]. The underlying disease of the recipient may affect this, since the larger thoracic cavity of an emphysematous patient may be more amenable to a larger donor lung, and a smaller lung may fit well in the thoracic cavity of a patient with pulmonary fibrosis. Additionally, oversized allografts may be better accommodated as a single than bilateral lung transplant because mediastinal shift allows more space for a single allograft in a small thoracic cavity.
In some cases, donors are ideal matches for recipients in many ways, except for size of the lung. In these cases, one alternative may be to perform a split lung bilateral lobar lung transplant or to downsize a large donor lung by lobectomy or wedge resection [30], although this may lead to poorer outcomes [31]. Additional information on size-matching at the time of procurement and the impact of size-matching on lung transplant outcomes are discussed elsewhere. (See "Lung transplantation: Donor lung procurement and preservation", section on 'Donor and recipient size matching'.)
Ideal donor criteria — Criteria based on expert opinion and transplant experience have been established for "ideal" donor candidates, although donors meeting all "ideal" donor criteria are uncommon (table 1) [32,33]. These criteria include: age less than 55 years, clear chest radiograph, arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) >300 mmHg at positive end-expiratory pressure (PEEP) 5, less than 20 pack year smoking history, absence of chest trauma, no evidence of aspiration or sepsis, no prior cardiopulmonary surgery, and absence of purulent secretions or gastric contents on bronchoscopic visualization prior to procuring the lungs.
Donors should be excluded if they are infected with HIV, human T-cell leukemia-lymphoma virus, or have active systemic viral infection (eg, measles, rabies, adenovirus, enterovirus, West Nile, and parvovirus), prion-related disease, or herpetic meningoencephalitis [34,35]. Certain other infections, including lower respiratory tract infections, may also make lung donation less desirable. (See 'Donor infection' below.)
Any donor satisfying ideal inclusion and exclusion criteria should be considered for lung donation.
Expanded donor criteria — Most potential organ donors do not meet the ideal lung donor criteria (table 1) [32], so many lung transplant programs use expanded criteria to increase the donor pool. When an extended criteria donor is being considered, effective communication between the organ procurement organization (OPO) coordinator and the transplant teams is essential. Each transplant team must know the original and current conditions of the donor. While outcomes for less-than-ideal criteria are acceptable, it is still the choice of the surgeon whether to accept a less-than-ideal donor lung. Some retrospective studies have examined outcomes for these expanded donor criteria [36-42].
Advanced donor age — Fifty-five years has been regarded as the upper age limit for an "ideal" candidate, based on the belief that accrual of comorbid conditions occurs as age increases [43]. Several studies have examined using lungs from older donors [38,39,44-52].
Results are mixed, with some indication of increased risk to the recipient, although other risk factors (such as ischemic time) may explain the difference. In a retrospective study of lung transplant recipients from January 2005 to June 2014 from the UNOS thoracic database, lungs from donors aged >60 years were utilized in 4 percent of recipients and were associated with a slightly worse five year (44 percent versus 52 percent, p<0.001) overall survival, although not among recipients older than 50 years [50]. No significant difference in survival was noted between recipients of lungs from young versus old donors when bilateral transplantation was performed.
Other studies have not shown a significant difference in outcomes when donors up to age 65 have been used [46,47]. A large retrospective analysis of 8860 lung allograft recipients from the Organ Procurement and Transplant Network (UNOS) database in the post lung allocation score (LAS) era (2005 to 2012) revealed no significant increase in one year graft failure among donors aged 55 to 64 compared with donors aged 18 to 54 [49].
In a single center retrospective study, no significant survival differences were detected when donor lungs ≥70 years were pre-selected for various criteria, including smoking status, oxygenation index, opacities on chest radiographs, and implanted in older recipients without pulmonary hypertension or idiopathic pulmonary fibrosis [47].
ABO compatibility — ABO-identical matches are preferred and may lead to a survival advantage over ABO-compatible matches. However, there is reported success using ABO-compatible rather than ABO-identical matches [53-56]. Lung transplant in the setting of ABO incompatibility is not recommended.
In a retrospective database study, the outcomes of 342 single lung recipients from ABO-compatible donors were compared with those of 3230 single lung transplant recipients from ABO identical donors [56]. Lungs from ABO-compatible donors were not associated with increased mortality (hazard ratio, 1.02, 95% CI 0.8-1.22). The two groups did not differ significantly in median length of stay, incidence of post-transplant airway dehiscence, or number of acute rejection episodes. While this study is reassuring regarding the use of ABO-compatible donors when ABO-identical matches are not available, further study is needed to determine the optimal immunosuppression in this setting and to clarify long-term outcomes.
A potential concern related to use of ABO-compatible lungs is the passenger leukocyte syndrome, in which donor B lymphocytes carried in the lung allograft release antibodies that react with recipient red blood cells, causing acute hemolysis [57,58]. The occurrence of the passenger leukocyte syndrome and post-transplant hemolysis could not be determined in the retrospective study described above [56]. (See "Kidney transplantation in adults: Anemia and the kidney transplant recipient", section on 'Later (>3 months) posttransplantation'.)
Abnormal chest radiograph — Patients with abnormalities on the chest radiograph should not be automatically rejected from donation [32]. If the lesion is unilateral, the unaffected lung may be used for transplant. Opacities on the chest radiograph should prompt early bronchoscopy to address the character and volume of secretions. Ventilator recruitment maneuvers may clear areas of atelectasis (see "Strategies to reduce postoperative pulmonary complications in adults", section on 'Lung expansion'). The combination of opacities on chest radiograph and purulent sputum on bronchoscopy was associated with a lower early survival in the transplant recipients in one series [39].
Low PaO2 — Several reports have examined using donors who do not start with an ideal PaO2 (PaO2 >300 mmHg on FiO2 = 1.0, PEEP = 5 cm H2O) [36,39,45,59]. While there are isolated reports of graft failure in this setting, others have reported no increased risk to the recipient [39,40,59]. If the PaO2 starts below goal, aggressive recruitment strategies should be used to increase the number of functional lung units (see "Overview of the management of postoperative pulmonary complications"). The same criteria should be applied at the end of the recruitment maneuver, and there must be evidence for a sustained benefit before the lungs are offered for donation.
Ex vivo lung perfusion techniques may be an acceptable method to salvage lungs that do not meet ideal PaO2 criteria due to pulmonary edema, thromboemboli, or contusions. (See 'Ex vivo lung perfusion' below and "Lung transplantation: Donor lung procurement and preservation", section on 'Normothermic ex-vivo perfusion (after cold static preservation)'.)
Diabetes mellitus — In a retrospective series of 10,333 lung transplantations performed in the United States, a donor history of diabetes was associated with an increase in mortality [40]. Diabetes has not traditionally been a criterion for donor lung exclusion, so further study of this potential risk factor for decreased lung transplant recipient survival is needed.
Smoking — The two main concerns for transplantation of lungs from a donor with a substantial smoking history are the potential for adverse effects on post-transplant lung function/survival and the transmission of cancer that is not evident on chest radiograph [40,43,60-65].
Generally, moderate to severe COPD or emphysema is apparent by history, oxygenation, ventilator mechanics, chest radiograph, or some combination of these. However, clinically inapparent effects of smoking may affect post-transplant survival.
●In a retrospective study of 510 transplant recipients who received lungs from donors with a smoking history compared with 712 recipients from nonsmoking donors, the three-year mortality was greater in those who received lungs from donors with a positive smoking history (adjusted HR 1.36, 95% CI, 1.11–1.67) [62]. The groups did not differ in baseline age or arterial blood oxygen tension. In addition, recipients of lungs from donors who had smoked had longer stays in the hospital and intensive care units than did those who received lungs from nonsmokers. On the other hand, receiving transplanted lungs from a donor with a smoking history is associated with a lower unadjusted hazard of death than remaining on the waiting list without a transplant (0.79, 95% CI 0.70-0.91).
●In a retrospective analysis of UNOS database from 2005 to 2011, use of lungs from heavy-smoking donors (HSDs; >20 pack-years) was not associated with increased mortality for single lung transplants (n=498), if the donor was not actively smoking (HR 0.84; 95% CI 0.59-1.19) [63] and double lung transplants (n=766), irrespective of whether the heavy smoking was current or former for the double lung cohort (HR 1.003; 95% CI, 0.867-1.161) [64]. Recipients with HSDs had longer median length of stay (23.0 versus 20.5 days, p = 0.001) for single lung transplant and (18.0 versus 17.0 days, p <0.001) for double lung transplant; and lower peak FEV1 after single-lung transplantation (80.1 versus 73.4 percent, p = 0.001), but similar peak FEV1 after double lung transplantation [63,64].
While there are case reports of bronchogenic carcinoma of donor origin in the transplanted lung, these are rare, and the donors had substantial smoking histories [43,60]. If the donor lungs are otherwise acceptable, increasing the donor pack-year limit will likely not increase the chances of a poor recipient outcome [40,61].
Malignancy — With a few exceptions a history of malignancy is an absolute contraindication to organ donation [32]. Low-grade skin cancer (not melanoma), carcinoma-in-situ (for example, of the cervix), and prostate cancer <Gleason 6 have an exceedingly low potential for metastasis and thus should not be exclusionary factors. Active (acute or chronic) leukemia, lymphoma, and plasmacytoma are unacceptable risks for organ donation. A history of melanoma is considered an absolute contraindication for organ donation [32].
Primary central nervous system (CNS) tumors are unlikely to have spread past the blood-brain barrier. However, high-grade tumors, particularly glioblastomas or medulloblastomas, are at increased risk of metastasis and may represent contraindications to transplant. Craniotomy, ventricular shunts, and radiation to the tumor also increase the chance of tumor spread [66].
Oncologist consultation is encouraged when there is uncertain transmission risk in the setting of malignancy (history or active). Informed consent should be obtained from the recipient prior to implantation.
Donor infection — Transmission of infection from the donor to the lung transplant recipient is a significant risk for the recipient (table 2) [34,67,68]. Certain donor infections do not limit transplant, provided the donor and recipient receive adequate treatment. In general, there is insufficient evidence to suggest that adequately treated donor infection with gram-positive or gram-negative pathogens affect outcomes; however, concern remains for infections including bacteremia or pneumonia with multidrug-resistant organisms. Invasive fungal disease is a contraindication.
●Bacterial and mycobacterial infections – Bacterial infections are the most problematic in the immediate postoperative period. Most centers administer empiric antibiotics to the recipient at the time of transplant and adjust these once results of intraoperative donor tracheal or bronchial aspirates are available [34]. In a retrospective case series, recipients of lungs that had potentially pathogenic bacteria cultured at the time of procurement spent significantly longer time on mechanical ventilation but without effect on 30 day mortality [69].
Organs from bacteremic donors generally result in few if any transmitted infections when the donor has received pathogen-specific antibiotics for a minimum of 48 hours before procurement [32].
Chest radiographs of potential donors should be screened for any evidence of active or prior Mycobacterial tuberculosis infection, which would exclude the patient as a transplant donor. Although transmission of M tuberculosis from donors has been reported in the absence of chest radiograph findings, more extensive testing for M tuberculosis is not feasible as it would delay organ procurement [70].
Active parasitic disease in the donor is a contraindication for the use of organs [71]. Donor derived transmission of Trypanosoma cruzi and Strongyloides stercoralis were reported, and targeted screening of donors coming from or with travel history to endemic areas by serologic testing is recommended [72].
●HIV, hepatitis C, hepatitis B – Transplant professionals and patients need to recognize that even comprehensive donor screening cannot detect all transmissible infections. Potential donors are screened for hepatitis C, hepatitis B surface antigen, hepatitis B core antibody positivity, and HIV. In addition to serologic testing, Nucleic Acid Amplification Testing (NAT) is used for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) to determine the viral load. The risk of HIV, HCV, or HBV transmission from a NAT negative donor organ is low (around 1 percent or less) [73]. (See "Infection in the solid organ transplant recipient", section on 'HIV, HTLV, and hepatitis viruses'.)
Directly acting antiviral agents (DAA) have demonstrated high cure rates for HCV in transplant recipients and the nonimmunosuppressed general population alike, raising the possibility that DAA might enable use of lungs from HCV-positive donors. In an observational study, pre-emptive DAA therapy (sofosbuvir-velpatasvir), administered for the first four weeks after transplantation, prevented development of HCV infection in 36 HCV-uninfected recipients who received lungs from HCV-positive donors [74]. While promising, this was a small study with short-term follow-up. In view of the high cure rates with new antiviral treatments, donors with hepatitis C ELISA positivity but NAT negative should no longer be excluded without discussion with the recipient. Even donors with true hepatitis C infection can be transplanted into a recipient who is hepatitis C positive [34]. (See "Infection in the solid organ transplant recipient", section on 'HIV, HTLV, and hepatitis viruses' and "Kidney transplantation in adults: Hepatitis C virus infection in kidney donors".)
A donor with active HBV, defined as positive HBV surface antigen (HBsAg) and/or detectable HBV NAT is expected to transmit the infection. Lung transplantation from donors with active HBV is seldom considered in nonendemic regions due to limited outcome data. Of the 271,593 organ transplants performed in the United States between January, 2009 and December, 2017, there were 25 events of donor-derived HBV transmission reported to UNOS; only one lung recipient seroconverted at 12 months [75]. The risk of HBV transmission to the lung recipient is low in the setting of hepatitis B core (HBc) antibody positivity alone with an undetectable viral load [76,77]. Potential causes of HBcAb positive, but nucleic acid test (NAT) negative, HBsAg negative, and HBsAb negative panel include (1) resolved infection, (2) false positive anti-HBc Ab, (3) occult chronic infection, or (4) resolving acute infection. For susceptible recipients (HBcAb negative, HBsAb negative) of lungs from donors with these results, antiviral prophylaxis for up to one year may be considered, although data are limited [76,78].
Lung recipients with adequate postvaccination HBsAb titers are at very low risk of HBV transmission and only require post-transplant monitoring if they receive lungs from an HBcAb positive donor. There are case reports of emergency transplantation from HBsAg positive donors with variable levels of serum HBV DNA to susceptible (HBsAg and HBcAb negative) recipients. Entecavir and HBIG were started immediately with excellent short-term clinical outcomes [79].
Individuals who are seronegative for HIV but meet high-risk behavioral criteria for HIV infection should not be excluded as organ donors, but the transplant team and potential recipient should be notified [32].
●Cytomegalovirus (CMV) – Although the presence of antibodies to cytomegalovirus was associated with increased mortality in a retrospective study of 10,333 lung transplants, this has not traditionally been considered an exclusionary donor criterion [40].
Routine prophylaxis against CMV infection has reduced the morbidity and mortality associated with CMV infection. While it is preferable to avoid transplanting lungs from CMV positive donors into CMV negative recipients, it is not always possible. Any donor or recipient with CMV positivity requires close monitoring in addition to CMV prophylaxis. (See "Prevention of cytomegalovirus infection in lung transplant recipients".)
●Other viruses – Parvovirus B19 transmission has led to red cell aplasia in the recipient, but this was treatable with intravenous immunoglobulin [34]. Donors with human herpes viruses 6-8, nonpulmonary herpes simplex, and varicella may be used with caution. (See "Viral infections following lung transplantation", section on 'Herpes viruses'.)
●West Nile virus – West Nile virus is a mosquito-borne virus that is endemic to most of the United States. Serology is prolonged beyond the period of transmission risk and the NAT is only transiently positive with reports of transmission in NAT-negative donors. Lungs from donors with unexplained active meningitis, encephalitis, or flaccid paralysis from regions with WNV activity should be declined. NAT and IgM testing can be performed after donation in circumstances of high clinical suspicion for WNV disease [72].
●Zika virus – No reports of confirmed cases of donor transmitted Zika virus infection exist to date, although Zika virus has been detected in a number of tissues and body fluids, raising the concern for transmission via transplantation. Diagnostics remain challenging and are available primarily in central reference laboratories. Current guidelines advise that donors with positive NAT test or clinical symptoms compatible with Zika should be excluded for 28 days from the positive test or the onset of symptoms. [80,81].
Concern for Zika or other emerging or endemic viral infections should not summarily exclude donors from transplantation; rather, the risk of donor derived infection should be balanced with the benefits of transplantation in each potential recipient. Consider consulting a transplant infectious disease expert for donors with symptoms, recent travel history, or other epidemiologic risk factors.
●Respiratory viruses – In general, lung donation from patients with respiratory viral infection (eg, influenza, parainfluenza, respiratory syncytial virus, adenovirus) of the lower respiratory tract is avoided. Screening of donors for most respiratory viruses (other than coronavirus disease 2019 [COVID-19]) with PCR or cross-sectional imaging is only recommended if there is clinical concern based on symptoms [71]. Guidelines advise declining lung donation from donors with imaging evidence of viral pneumonia [82]. Respiratory viral infection other than COVID-19 does not typically preclude transplantation of solid organs other than the lung.
●COVID-19 – The virology, clinical manifestations, diagnosis, and management of COVID-19 are described separately. (See "COVID-19: Epidemiology, virology, and prevention" and "COVID-19: Diagnosis" and "COVID-19: Management in hospitalized adults" and "COVID-19: Management of the intubated adult".)
Transmission of SARS-CoV-2 via a lung allograft has been reported from donors who initially tested negative by nasal swab but were later confirmed positive on a lower respiratory tract sample [83,84]. In response, the Organ Procurement and Transplantation Network (OPTN) has mandated that all potential lung donors undergo testing of a lower respiratory tract specimen (eg, tracheal aspirate, bronchoscopic washing, or bronchoalveolar lavage) for SARS-CoV-2 by nucleic acid test (NAT) in addition to screening by symptoms, exposures, and upper respiratory tract sampling [85]. The accuracy of NAAT is discussed in greater detail separately. (See "COVID-19: Diagnosis", section on 'NAAT (including RT-PCR)'.)
As SARS-CoV-2 infection has the potential to cause pneumonia, diffuse alveolar damage, alveolar hemorrhage, and death in lung-transplant recipients, deceased donors with known or suspected COVID-19 within the past 21 days, a positive NAT for SARS-CoV-2, or a high likelihood of SARS-CoV-2 infection based on symptoms or imaging should not be used for lung transplantation [82]. Caution is advisable for potential donors with known contact with a confirmed or suspected case, travel to or residence in an area of high risk of transmission within 14 days, or symptoms of fever, influenza-like illness, or pneumonia regardless of exposure within the past 14 days. However, the risk of disease transmission and its possible adverse impact on the outcome of transplantation should be weighed against the risk of death for the potential recipient if that opportunity for transplantation is missed [86]. The general screening of potential organ donors for SARS-CoV-2 is described separately. (See "COVID-19: Issues related to solid organ transplantation".)
Potential donors with a positive COVID test more than 21 days prior to organ harvest, negative lower respiratory tract PCR, lack of hypercoagulability or hyperinflammatory syndrome during the terminal hospitalization, and negative imaging for viral pneumonia may be appropriate candidates for thoracic organ donation [87], although experience with lung transplantation under these conditions is very limited.
Ex vivo lung perfusion — Complications such as pulmonary edema, contusions, and vascular thrombosis have typically rendered donor lungs unacceptable for transplantation, thereby reducing the supply of donor lungs. Efforts to improve the quality, and therefore the quantity, of lungs available for transplantation are ongoing. Ex vivo lung perfusion (EVLP, also known as ex vivo reconditioning) is being explored as a way to increase the number of acceptable lungs and is described separately. (See "Lung transplantation: Donor lung procurement and preservation", section on 'Normothermic ex-vivo perfusion (after cold static preservation)'.)
Future directions
Donor genetics — Gene expression microarray technology has been used to find molecular markers that predict primary graft dysfunction (PGD) in transplant recipients. In a case-control study, gene microarrays of 10 donor lungs that developed PGD were compared with 16 controls with a favorable outcome; four upregulated genes, ATP11B, FGFR2, EGLN1, and MCPH1, were associated with development of PGD [88]. Such biologic signatures may in the future supplement clinical criteria used at the preimplantation evaluation and selection stage to predict post-transplant complications, such as primary graft dysfunction, and help guide therapy in the immediate post-transplant period.
Gene therapy is also being investigated as a potential strategy to increase the number of donor lungs. Injured human lungs that were considered to be unsuitable for clinical use were treated with adenoviral mediated human interleukin (IL)-10 gene therapy. After preservation ex-vivo at body temperature, the IL-10 treated lungs showed reduced markers of inflammation and improved function (PaO2 and pulmonary vascular resistance) compared with control untreated lungs [89].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lung transplantation".)
SUMMARY AND RECOMMENDATIONS
●Donation types – The majority of transplanted lungs are donated after brain death, although a small portion are donated after circulatory death (DCD). Donation after circulatory death follows detailed protocols to ensure circulatory death prior to procurement and to increase the chances of successful organ recovery. (See 'Donation after brain death' above and 'Donation after circulatory death' above.)
●Outcomes based on donation type – As experience with lung DCD increases, observational studies show equivalent long-term outcomes compared with those of donation after brain death. (See 'Outcomes based on donation type' above.)
●Ideal donor criteria – Ideal donors for lung transplant are less than 55 years of age, have smoked less than 20 pack years, have a normal chest radiograph, near normal gas exchange, and absence of chest trauma, prior cardiothoracic surgery, known aspiration, sepsis, or purulent respiratory secretions. (See 'Ideal donor criteria' above.)
●Use of organs from donors not meeting ideal donor criteria – Several retrospective series have examined recipient outcomes after use of donor lungs that do not meet ideal donor criteria and have found that outcomes for "expanded" donor criteria are only slightly worse than those for "ideal" organs. (See 'Expanded donor criteria' above.)
•Mildly impaired lung function – When donor lungs are less than ideal (eg, PaO2:FiO2 <300 mmHg, radiographic pulmonary edema), recruitment maneuvers and/or several hours of normothermic ex vivo lung perfusion (EVLP) may allow functional recovery and safe use of these lungs. (See 'Abnormal chest radiograph' above and 'Low PaO2' above and 'Ex vivo lung perfusion' above.)
•Donors with a heavy smoking history – The main concern about using lungs from donors who have a tobacco smoking history of greater than 20 pack years is the possibility of transmission of bronchogenic cancer to the recipient. Usually, significant chronic obstructive pulmonary disease (COPD) can be detected by a history of respiratory symptoms, abnormality of chest imaging, and abnormal ventilator mechanics. (See 'Smoking' above.)
•Malignancy – Malignancy is generally an absolute contraindication for organ donation, unless an adequate disease-free interval has elapsed or the malignancy is of extremely low potential for metastasis (eg, carcinoma in situ of the cervix or some low grade nonmelanoma skin cancers). (See 'Malignancy' above.)
•Infection – Transmission of infection from the donor to the lung transplant recipient is a significant risk for the recipient; infections that exclude an individual from being an organ donor or require specific intervention are listed in the table (table 2). (See 'Donor infection' above.)
ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Pamela McShane, MD, and Edward Garrity, MD, MBA, who contributed to earlier versions of this topic review.
