INTRODUCTION — Optimal selection and care of donor lungs for transplant are needed to increase the number of available lungs. Deceased donor evaluation, selection, and management after brain and cardiac death will be reviewed here from the lung transplant perspective. Living donor lobar transplants are rare in comparison to deceased donor lung transplants.

The indications for lung transplantation, selection of lung transplant recipients, and donor lung preservation are discussed separately. (See "Lung transplantation: An overview" and "Lung transplantation: Donor lung procurement and preservation" and "Evaluation of the potential deceased organ donor (adult)" and "Management of the deceased organ donor" and "Lung transplantation: General guidelines for recipient selection".)

PANDEMIC CORONAVIRUS DISEASE 2019 (COVID-19) — Coronavirus disease 2019 (COVID-2019) due to the novel and highly infectious RNA coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world [1,2]. 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 [3,4]. 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 [5]. Evidence in favor of greater sensitivity of lower respiratory tract samples comes includes a series of 205 patients with a COVID-19 diagnosis based on the clinical symptoms and radiological changes in whom bronchoalveolar lavage fluid specimens showed the highest positive rates (14 of 15; 93 percent), followed by sputum (72 of 104; 72 percent), nasal swabs (5 of 8; 63 percent), and pharyngeal swabs (126 of 398; 32 percent) [6]. The accuracy of NAT is discussed in greater detail separately. (See "COVID-19: Diagnosis", section on 'NAAT (including RT-PCR) to diagnose current infection'.)

As SARS-CoV-2 infection has the potential to cause pneumonia, diffuse alveolar damage, alveolar hemorrhage, and death in the recipient, 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 should not be used for lung transplantation in our opinion [7]. Caution is advisable for potential donors with known contact with a confirmed or suspected case, travel to or residence in an area of known local 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 [8]. The general screening of potential organ donors for SARS-CoV-2 is described separately. (See "COVID-19: Issues related to solid organ transplantation".)

Given the limitations in the RT-PCR testing, we suggest obtaining chest computed tomography (CT) of potential lung donors; a chest CT may reveal signs of COVID-19 (eg, ground glass or consolidative opacities) before development of symptoms [7,9,10]. In one study of 1014 patients in Wuhan, China, approximately 70 percent of patients with negative RT-PCR tests had typical CT manifestations [11]. Current guidelines advise declining a donor with imaging findings of viral pneumonia [7].

Evolving travel restrictions continue to reshape the procurement process. On March 28, 2020 UNOS issued a communication strongly encouraging recovery of organs by local teams [12].

DONATION AFTER 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 [13]. (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 [14]. 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 DETERMINATION OF DEATH — Some experts recommend that the phrase "donation after circulatory determination of death" (DCDD) replace "donation after cardiac death" or "nonbeating heart donation." These experts emphasize that organ donation occurs after cessation of circulatory and respiratory, not cardiac, function [15]. There is no official consensus to change this terminology, however.

DCDD has become an accepted method of increasing the donor pool in some transplant centers and organ procurement organizations (OPO) [16], 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 2003 [17,18]:

●I Dead on arrival to hospital

●II Unsuccessful resuscitation

●III Awaiting cardiac arrest (inpatient withdrawal of support)

●IV Cardiac arrest after brain-stem death

●V Cardiac arrest in a hospital inpatient

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 [19,20]. Up to 20 to 30 percent of all lung transplants come from DCDD in Australian and European centers [21]. However DCDD 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 (OPTN) annual data report, almost 6 percent of lung transplant recipients received lungs from DCDD donors in 2019 [22].

Situations in which DCDD may be considered include irreversible brain injury, end stage musculoskeletal disease, and high spinal cord injury [23,24]. These criteria may be used when the donor does not meet criteria for brain death (see 'Donation after brain death' above). Other situations include sudden death without significant thoracic or abdominal trauma, known time of cardiac arrest, and cardiopulmonary resuscitation maneuvers started within 15 minutes of cardiac arrest [23].

The details of protocols and management recommendations for DCDD have been the subject of a consensus conference [23].

●By definition, death precedes organ procurement and requires cardiopulmonary criteria to prove absence of circulation [25,26].

●Determination of death must meet criteria for irreversible cessation of function; procurement of organs should not cause death of the donor [25,26].

●The main criterion for cardiac death is absence of circulation, which may be assessed via an indwelling arterial line or Doppler study.

●Electrocardiographic (ECG) silence is not a necessary criterion in the absence of circulation, but may be used as a confirmatory test; ECG silence alone is adequate evidence that circulation has ceased.

●The conference concluded that after cessation of circulation "at least two minutes of observation is required, and more than five minutes is not recommended" for declaration of death.

●The American Thoracic Society (ATS) states that ante mortem interventions such as obtaining blood samples, performance of bronchoscopy, injection of heparin or phentolamine and femoral cannulation are ethically appropriate if they contribute to good transplant outcomes and have a low chance of harming a prospective donor [20].

●In the setting of withdrawal of life sustaining treatment, the time limit to cardiac 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 for a better understanding of the optimal 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)'.)

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 and will coordinate evaluation of the donor's suitability for transplant. (See "Lung transplantation: An overview".)

OUTCOMES — Comparison of lung transplantation graft survival after donation after circulatory determination of death (DCDD) compared with donation after brain death has revealed comparable results.

●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 donation after DCDD and donation after brain death (DBD) [21,27].

●In a subsequent six-year single center study that included 60 transplants from DCDD donors, there was a higher incidence of primary graft dysfunction grade 3 at the end of the procedure and higher risk of bronchiolitis obliterans syndrome (BOS) in the long-term follow-up; however, the overall cumulative survival was not significantly different [28].

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 [29]. 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 cardiac death to transplantation are key to the success of donation after cardiac death. 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, so that all teams are ready to recover 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 [30,31]. 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 [32]. 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.

The use of oversized donor lungs (ie, slightly larger than predicted by recipient size) may reduce the risk of developing grade 3 primary graft dysfunction (PGD3) at any point within 72 hours of lung transplantation. Among 812 patients who underwent bilateral lung transplantation between 2002 and 2010, use of oversized donor lungs was associated with a lower odds ratio of PGD3 (adjusted OR 0.58, 95% CI 0.38-0.88), compared with using undersized lungs, but this effect was limited to recipients without chronic obstructive pulmonary disease (COPD) [33]. However, given current donor organ shortage and waitlist mortality, it is not practical to intentionally oversize most allografts. (See "Primary lung graft dysfunction".)

The effect of lung size mismatch on the risk of bronchiolitis obliterans syndrome (BOS) was examined in 159 adult bilateral lung transplant recipients [30]. Assessment of size matching was based on predicted values for gender and height. At one and six months, recipients with "oversized" lungs had higher expiratory airflow capacity based on higher ratios of forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC), than those with "undersized" lungs. The probability of developing BOS, defined as a decrease of more than 20 percent from the highest post-transplant FEV₁, was lower among those with oversized lungs. Further study is needed to determine the effects of lung size mismatch. (See "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome".)

In some cases, donors are ideal matches for recipients in many ways, except for size of the lung. In these cases, an alternative may be to perform a split lung bilateral lobar lung transplant or to downsize a large donor lung by lobectomy or wedge resection [34]. (See "Lung transplantation: Disease-based choice of procedure".)

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) [35,36]. 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 [37,38]. Certain other infections may also make organ donation less desirable. (See 'Donor infection' below.)

Any donor satisfying these 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) [35], 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 [39-45].

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 [46]. Several studies have examined using lungs from older donors [41,42,47-55].

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 [53]. 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 [49,50]. 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 [52].

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 [50].

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 [56-59]. 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 [59]. 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 [60,61]. The occurrence of the passenger leukocyte syndrome and post-transplant hemolysis could not be determined in the retrospective study described above [59]. (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 [35]. 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 [42].

Cytomegalovirus antibodies — The presence of antibodies to cytomegalovirus was associated with increased mortality in a retrospective study of 10,333 lung transplants, although this has not traditionally been considered an exclusionary donor criterion [43]. Further study of this potential risk factor for decreased lung transplant recipient survival is needed.

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) [39,42,48,62]. While there are isolated reports of graft failure in this setting, others have reported no increased risk to the recipient [42,43,62]. 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 [43]. 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 [43,46,63-68].

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) [65]. 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) [66] 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) [67]. 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 [66,67].

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 [46,63]. If the donor lungs are otherwise acceptable, increasing the donor pack-year limit will likely not increase the chances of a poor recipient outcome [43,64].

Malignancy — With a few exceptions a history of malignancy is an absolute contraindication to organ donation [35]. Low-grade skin cancer (not melanoma) and carcinoma-in-situ (for example, of the cervix) have an exceedingly low potential for metastasis and thus should not be exclusionary factors. A history of melanoma is considered an absolute contraindication for organ donation [35].

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 [69].

Donor infection — Transmission of infection from the donor to the lung transplant recipient is a significant risk for the recipient (table 2) [37,70]. Certain donor infections do not limit transplant, provided the donor and recipient receive adequate treatment. In general, donor infection with gram positive organisms appears to affect outcomes less than gram negative infections. 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 [37]. 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 [71].

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 [35].

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 [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 [37]. (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".)

The risk of virus transmission is low in the setting of hepatitis B core (HBc) antibody positivity, negative surface antibody (HBsAb), and an undetectable viral load [75]. 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 such lung allograft donors, antiviral prophylaxis for up to one year may be considered, although data are limited [75,76].

Patients 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 [35].

●Cytomegalovirus (CMV) – Routine prophylaxis against CMV infection has reduced the morbidity and mortality associated with this infection. While it is preferable to avoid transplanting lungs from CMV positive donors into CMV negative recipients, it is not always possible. CMV negative recipients who receive a lung allograft from a CMV-positive donor require close monitoring in addition to CMV prophylaxis. (See "Prevention of cytomegalovirus infection in lung transplant recipients".)

●Respiratory virus infection – In general, lung donation from patients with respiratory viral infection (eg, influenza, parainfluenza, respiratory syncytial virus, adenovirus) of the lower respiratory tract is avoided.

●Other viruses – Parvovirus B19 transmission has led to red cell aplasia in the recipient, but this was treatable with intravenous immunoglobulin [37]. Donors with human herpes viruses 6-8, simplex, and varicella may be used with caution. (See "Viral infections following lung transplantation", section on 'Herpes viruses'.)

●Zika virus – Zika virus has been detected in a number of tissues and body fluids, raising the concern that Zika virus could be transmitted via transplantation. Diagnostics remain challenging and are available primarily in central reference laboratories. The Organ Procurement and Transplantation Network (OPTN)/UNOS Ad Hoc Disease Transmission Advisory Committee (DTAC), the American Society of Transplantation (AST), and the American Society of Transplant Surgeons (ASTS) have reviewed the potential risk of recent Zika virus infection on solid organ transplantation. They advise that donor deferral should be considered if there is history of travel to Zika-endemic areas in the 28 days prior to donation [77].

In the case of potential living donors with Zika infection, donation should be deferred where possible. The deferral period may be adjusted as more is learned about length of time that Zika can persist in tissues or when a diagnostic test becomes available that can determine current or recent infection. It has been suggested that donor organs should not be used from individuals with symptoms suggestive of Zika virus infection and travel to an area of Zika transmission in the prior six months, unless symptoms can be attributed to another condition that does not preclude donation [78].

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)'.)

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 [79]. 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 [80].

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: Liver transplantation" and "Society guideline links: Lung transplantation".)

SUMMARY AND RECOMMENDATIONS

●The majority of transplanted lungs are donated after brain death, although a small portion are donated after circulatory determination of death (DCDD, also known as cardiac death). (See 'Donation after brain death' above.)

●The experience with lung donation after DCDD is increasing, and some studies show equivalent long-term outcomes compared with those of donation after brain death. (See 'Donation after circulatory determination of death' above.)

●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.)

●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.)

●Ideally, the donor should have an arterial oxygen tension (PaO₂) >300 mmHg on fraction of inspired oxygen (FiO₂) = 1.0, positive end-expiratory pressure (PEEP) = 5 cm H₂O. When donor lungs are less than ideal (eg, PaO₂:FiO₂ <300 mmHg, radiographic pulmonary edema, DCDD Maastricht score III or IV), several hours of normothermic ex vivo lung perfusion (EVLP) may allow safe use of these lungs. (See 'Donation after circulatory determination of death' above and 'Donor selection' above.)

●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 radiograph, and abnormal ventilator mechanics. (See 'Smoking' above.)

●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.)

●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.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Pamela McShane, MD, and Edward Garrity, MD, MBA, who contributed to earlier versions of this topic review.