Lung transplantation and end-stage lung disease

• Lung transplantation is the definitive treatment for selected patients with end-stage lung disease whose gas exchange, symptoms and quality of life do not improve enough with medicines, oxygen, rehabilitation or lung volume reduction.
• It is a scarce, high-risk resource. The 2021 international consensus considers adults only when the risk of death from lung disease exceeds 50% within 2 years without transplant, and the expected 5-year post-transplant survival exceeds 80% from a general medical perspective.^[1]
• Timing matters more than emergency rescue: patients are referred early, before they meet listing criteria, so modifiable barriers can be fixed and vaccines completed.^[1]
• Median survival after transplant is about 6 years in adults, and chronic lung allograft dysfunction (CLAD) affects about half of recipients by 5 years.^[2]
• Complications are common and multisystem: primary graft dysfunction, rejection, infection, airway stenosis, kidney failure, diabetes and malignancy.^[5]
• Palliative care is not only end-of-life care: guidelines call for early, needs-based integration into routine care for COPD and interstitial lung disease, alongside disease treatment.^[3][4]

By the end of this page you should be able to:

1. State the general and disease-specific indications and referral triggers for adult lung transplantation.
2. Decide when to refer, evaluate and list a patient, and recognise what is too early versus too late.
3. Explain the absolute and relative contraindications and how risk factors interact.
4. Describe the surgical approach, the three anastomoses and the reperfusion strategy.
5. Outline the immediate aftercare and the major medical, surgical and drug-related complications.
6. Define CLAD and its BOS and RAS phenotypes, including diagnostic cut-offs and staging.
7. Integrate palliative care into chronic lung disease care, including advance care planning.
8. Adjust assessment for children, older adults, multi-organ disease and low-resource settings.

End-stage lung disease is advanced, progressive respiratory failure that no longer responds to maximal conventional treatment, whether the underlying disease is obstructive (COPD), fibrotic (idiopathic pulmonary fibrosis and other interstitial lung diseases), suppurative (cystic fibrosis and non-cystic fibrosis bronchiectasis) or vascular (pulmonary arterial hypertension). In practice it is defined functionally: a patient who remains severely breathless, hypoxaemic or hypercapnic, exercise-limited and often depressed, with an unacceptable quality of life and a short predicted survival, despite best therapy. Lung transplantation is the only option that restores adequate gas exchange and improves both survival and quality of life in such patients.

Worldwide about 4,500 lung transplants were performed in 2019 at more than 260 centres.^[1] COPD is the commonest indication (about 40% of transplants worldwide), followed by interstitial lung disease.^[6] Survival has improved, but it remains worse than for other solid-organ transplants: median survival is about 6 years in adults (about 5.5 years in children) in one review and about 6.7 years in another.^[2][5] A registry-based review puts the cumulative incidence of CLAD at about 22% at 2 years, 50% at 5 years and 77% at 10 years after transplant.^[2] These figures should frame honest counselling: transplant buys time and quality of life, not a normal lifespan.

This topic follows the whole pathway: when to think of transplant, how referral and listing are timed, what contraindications matter, what the operation involves, what complications follow, and how palliative care runs alongside all of it.

The underlying principle is that donor lungs are a scarce societal resource, so candidates are those who gain the greatest net survival and who will not expose the graft to unacceptable risk. The 2021 ISHLT consensus states that lung transplantation should be considered for adults with chronic, end-stage lung disease meeting the following general criteria.^[1]

• A high (more than 50%) risk of death from lung disease within 2 years if transplantation is not performed.
• A high (more than 80%) likelihood of 5-year post-transplant survival from a general medical perspective, provided graft function is adequate. ^[1]

An earlier consensus document, reflected in a 2018 review of indications, required a third criterion: a high (more than 80%) likelihood of surviving at least 90 days after transplantation.^[6] The 2021 document no longer lists 90-day survival as a separate general criterion, although its contraindication and risk-factor tables still exclude patients unlikely to survive the early postoperative period. Both sources agree that these are threshold judgements made case by case, not rigid cut-offs.^[1][6]

Each disease has its own referral (evaluation) and listing (active wait-listing) triggers. The tables are condensed from the 2021 ISHLT consensus as presented in a 2022 update.^[7]

Survival data explain why these thresholds matter. Idiopathic pulmonary fibrosis carries median survival of 2 to 3 years from diagnosis, and only 20 to 30% of patients survive more than 5 years; with an FEV1 under 30% predicted, cystic fibrosis is associated with median survival of 6.6 years in one study.^[6][7] In cystic fibrosis, an FEV1 under 30% predicted was associated with 2-year mortality of about 40% in men and 55% in women.^{[6] [1]}

Transplant is not an emergency rescue but a planned process, and early, controlled referral improves results. The 2021 consensus recommends that referral begin before the patient meets listing criteria, so that transplant (its requirements and outcomes) can be discussed and modifiable barriers (obesity, malnutrition, comorbidities, social support) addressed.^[1] Early referral also allows vaccines to be given when they still work: some require multiple doses, live vaccines are forbidden after transplant, and any vaccine is less protective once the patient is immunosuppressed.^[1]

Disease-specific timing follows the same "refer early" principle. Interstitial lung disease, especially idiopathic pulmonary fibrosis, risks acute exacerbation and abrupt failure, so referral at diagnosis is advised.^[6] Cystic fibrosis candidates should be reviewed early in decline, with attention to younger women with rapid loss of function.^[1] For pulmonary arterial hypertension, early referral is preferred, particularly in children with idiopathic disease, before decompensation.^[1][7]

Referral that is "too early" is harmless: the centre gives re-referral criteria and optimisation advice rather than listing the patient.^[1] Referral that is "too late" is dangerous: prehabilitation and preparation are missed, and patients arrive ventilated or on ECLS as a bridge to transplant, with worse outcomes.^[1]

The 2021 consensus explicitly links the two halves of this topic: "When referring for lung transplant evaluation, consider simultaneous referral to palliative care to provide decision support and treatment selection that is consistent with goals of care throughout the transplant evaluation, listing, surgery, and post-transplant."^[1]

Contraindications are risk categories rather than absolute rules, and the 2021 consensus divides them into absolute contraindications, high-risk factors and risk factors with unfavourable implications.^[1] Risk factors are "thought to be possibly multiplicative" when several coexist, and whether a candidate is acceptable depends on the centre's expertise with that combination.^[1] Before refusing, the referrer should communicate directly with at least one programme experienced with that contraindication.^[1]

• Unwillingness to accept transplant, or failure to understand the disease and transplant despite teaching.
• Malignancy with high risk of recurrence or death from cancer (often 2 years disease-free for low-risk skin cancers and 5 years for most others, individualised, with oncology input).^[6]
• Severe dysfunction of another organ: glomerular filtration rate under 40 mL/min/1.73 m2, cirrhosis with portal hypertension or synthetic dysfunction, acute liver or renal failure, acute coronary syndrome within 30 days, unless multi-organ transplantation is considered. ^[1]
• Stroke within 30 days; acute sepsis, septic shock, active extrapulmonary or disseminated infection, active tuberculosis. ^[1]
• HIV infection with detectable viral load. ^[1]
• Limited functional status with poor potential for rehabilitation; progressive cognitive impairment or dementia.
• Repeated non-adherence without improvement (in adults); active substance use including tobacco, vaping, marijuana smoking or intravenous drugs.
• Uncontrolled conditions expected to limit post-transplant survival, including chest wall or spinal deformity causing severe restriction, and class II/III obesity (BMI 35 kg/m2 or above).

• Age 65 to 70 is a risk factor and age over 70 high or substantially increased risk. There is no absolute age limit, and older recipients are increasingly accepted, but older patients have worse long-term survival; age and comorbidity together matter more than age alone.^[1][6]
• BMI 30 to 34.9, 16 to 17, under 16, or 35 and above at different levels. Obesity links to primary graft dysfunction and mortality, especially above 35. Underweight is a risk factor, although cystic fibrosis recipients with BMI below 17 can still have acceptable survival.^[1]
• Coronary artery disease (even mild to moderate), previous CABG, peripheral vascular disease, reduced left ventricular ejection fraction (under 40% as high risk; 40-50% as a risk factor).
• Connective tissue disease, severe gastro-oesophageal reflux, oesophageal dysmotility, untreated haematological disorders, telomeropathy, hypoalbuminaemia below 3.5 g/dL, osteoporosis, poorly controlled diabetes on insulin, frailty.
• Prior thoracic surgery or pleurodesis (more bleeding and early morbidity, but not contraindications).
• Infection with resistant organisms: Mycobacterium abscessus, Burkholderia cenocepacia or gladioli, Scedosporium apiospermum, Lomentospora prolificans; best managed at experienced centres.
• Extracorporeal life support or mechanical ventilation before transplant: once relative contraindications, but carefully selected patients can be bridged successfully, especially when awake and mobile.^[6][1]
• Chest wall or spinal deformity and malignancy, addressed above.

Malignancy deserves a closer look. It is an absolute contraindication when recurrence or death from cancer is highly likely. But not all neoplasms are equal: dysplasia of the cervix or anus and non-melanoma skin cancer may be managed after transplant with intensive surveillance; transplant can be considered when the stage-specific risk of recurrence is very low after negative metastatic evaluation and an appropriate cancer-free interval, in close collaboration with oncology.^[1] Tobacco, vaping, marijuana smoking and intravenous drug use require documented abstinence, and abstinence of 6 months or less carries a higher relapse risk (so duration is tailored to medical acuity).^[1] For HIV, hepatitis B and C, transplant is possible if the infection is controlled or treated and significant liver fibrosis is absent.^[1]

Psychosocial assessment is probabilistic, not exclusionary: socioeconomic factors must not be used to exclude a patient from candidacy. Inadequate support raises risk and should trigger enhanced surveillance rather than refusal.^[1]

The surgeon operates in the mediastinum and both pleural cavities. Key structures are the trachea and main bronchi (whose bronchial arteries are usually not revascularised, so the bronchus is deliberately short, with revascularisation typically taking 2 to 4 weeks), the pulmonary arteries and their branches, the left atrial cuffs formed from the pulmonary veins, and the phrenic, vagus and recurrent laryngeal nerves. The pericardium, pulmonary ligaments and pleural adhesions can be dense in patients after pleurodesis or previous surgery. Because the donor's left atrial cuff is frequently inadequate, the pulmonary veins must be divided with enough cuff preserved; the thin left atrial wall is easily injured, especially on the right, where an interatrial groove is developed.^[8]

Bronchial and vascular size mismatch in single-lung transplant can be accommodated by telescoping the bronchus one cartilage ring deep, or by patching the artery or atrial cuff.^[8] The recurrent laryngeal nerve on the left and the phrenic nerve on the right are vulnerable, particularly with adhesions.^[8]

A standard set-up includes a clamshell incision (fourth intercostal space, anterior axillary line to sternum) with sternal division, or less commonly bilateral anterolateral thoracotomy or median sternotomy; cardiopulmonary bypass (CPB) or central/peripheral ECMO support; transoesophageal echocardiography; bronchoscopy and video bronchoscopy; a pulmonary-artery catheter; pleural and pericardial drains; perfusion solutions and back-table tools for cuff reconstruction; and a femoral cannulation set should ECMO be needed urgently.^[8]

ECMO is preferred to CPB by many teams because it needs less heparin, produces a smaller systemic inflammatory response, needs fewer transfusions and can be continued before or after the operation.^[8] CPB is still required when haemodynamic instability persists despite ECMO, when severe hypoxaemia or hypercapnia occurs on an injured lung, or when a simultaneous cardiac operation is needed.^[8]

Preparation is a programme of optimisation, not a checklist. Candidate education covers transplant, its requirements and expected outcomes. Vaccination records are reviewed and vaccines completed before transplant if possible. Age-appropriate and disease-specific cancer screening is performed. Renal, cardiac (including coronary), hepatic, nutritional and frailty evaluation, psychosocial assessment and microbiological profiling of donor and recipient flora all precede listing. Informed consent must be capacity-based; in children, assent must be developmentally appropriate.^[1]

For cystic fibrosis and bronchiectasis candidates, sinus disease and nutrition are addressed; for autoimmune candidates, multidisciplinary assessment by rheumatology, gastroenterology and nephrology is standard.^[1] Candidates with a substance-use history enrol in treatment and demonstrate abstinence with serial screening before transplantation.^[1] The allocation system (urgency-based scores such as the Lung Allocation Score in the United States) determines access to donor organs.^[6]

Bilateral sequential lung transplantation is used here as the model because it shows the core principles; single-lung transplant is simpler, and heart-lung transplant is reserved for disease involving both organs. The operation is lengthy, with implantation dominated by the sequential anastomoses.

The patient is supine, arms elevated or abducted to expose the thorax but not enough to risk brachial plexus injury, with a cushion under the mid-thorax to help hilum exposure. The inguinal regions are prepared so ECMO can be established quickly if needed.^[8]

The commonest approach is a clamshell incision along the fourth intercostal space from the anterior axillary line to the sternum, with sternal division, giving generous exposure of both pleural cavities, mediastinum and heart. In women, dissection follows the inframammary lines with breast tissue mobilised above the pectoralis major. Alternatives are bilateral anterolateral thoracotomy, which preserves the sternum and suits COPD patients with large cavities and good right heart function, and median sternotomy, which gives limited pleural access but avoids chest-wall morbidity.^[8]

Adhesiolysis is done as completely as possible before heparin is given, to limit bleeding; phrenic and vagus nerves are protected throughout; and small systemic collaterals are ligated when the inferior pulmonary ligament is divided.^[8]

The pulmonary artery is dissected and divided beyond the first bifurcation to leave a long, size-corrected stump; the pulmonary veins beyond the first lobar branch so that an adequate atrial cuff remains; and the bronchus just proximal to the upper lobar bronchus, preserving as much peribronchial tissue as possible to protect the bronchial blood supply. Bronchial artery and adjacent nodal arteries are ligated or divided carefully.^[8]

On the right, the left atrial wall is often very thin, so an interatrial groove is developed carefully. In restrictive disease a small cavity and raised diaphragm can make right-sided implantation difficult; a stitch in the diaphragm drawn through an intercostal space can pull it down to make room.^[8]

For patients with severe pulmonary hypertension and right heart dysfunction, cardiac support is started before one-lung ventilation; dividing the pulmonary artery of the first (injured) lung reduces shunt, and severe hypoxia from a major air leak is managed by rapid one-lung ventilation or manual compression.^[8] Cardiopulmonary support also gives controlled reperfusion and prevents "first lung syndrome" (hyperperfusion of the first graft while the second is implanted).^[8]

The first lung implanted is usually the one with least perfusion, or the most damaged if no cardiopulmonary support is used.^[8]

Anastomoses are performed in the order bronchus, then pulmonary artery, then left atrial cuff.^[8]

• Bronchial anastomosis: a single running 4-0 polydioxanone suture, end-to-end, with telescoping one cartilage ring deep for severe size mismatch. Routine bronchoscopy and an air-leak test follow. Revascularisation of the donor bronchus takes 2 to 4 weeks; a short bronchus limits bronchial ischaemia. After transplant, airway complications are the commonest complication.^[8]
• Pulmonary artery anastomosis: a single 6-0 Prolene running suture, knotted after the artery is filled with heparin solution; brief proximal declamping while the distal artery is clamped tests the join. Mismatch can be handled by tacks, stapling or pericardial patch, or by anastomosing just distal to the first branch. Stenosis is rare in adults, but long stumps may kink.^[8]
• Left atrial cuff anastomosis: a single 5-0 Prolene running suture, everting mattress posteriorly to reduce thrombus along the suture line and simple running anteriorly. De-airing is by knotting only after partial declamping, slowly expelling blood and air for at least 2 to 3 minutes under moderate ventilation. Stenosis of the left atrial cuff causes venous congestion, one of the most devastating complications, so the pulse-string effect must be avoided.^[8]

Adequate cuff tissue is needed on both sides; if the donor cuff is short, native-tissue suture or pericardial reconstruction is used.^[8]

Controlled reperfusion with protective ventilation is the key to avoiding ischaemia-reperfusion injury and primary graft dysfunction. Endothelial membranes stiffen during cold storage, so rapid reperfusion is stressful; the pulmonary artery clamp is released gradually over at least 10 minutes when there is no cardiopulmonary support.^[8] With ECMO, low perfusion pressure and low flow are maintained easily, and flow is not run at full capacity while the second lung is implanted, to avoid warm ischaemia of the first graft.^[8] A protective strategy (low tidal volume, adequate positive end-expiratory pressure, low fraction of inspired oxygen) is used, and steroids and mannitol may be given at reperfusion to limit injury.^[8]

Each pleural cavity receives one right-angled and one straight tube, plus a right-angled tube in the pericardial cavity. In grossly oversized grafts, wedge resection of the right middle lobe and lingula, or delayed chest closure, can ease haemodynamics and prevent atelectasis. The sternum is closed with Kirschner wire or heavy Vicryl sutures.^[8]

After transplant the patient goes to intensive care, remains ventilated until conscious with adequate lung function, then is weaned, with careful pain control, meticulous fluid and haemodynamic management and immediate anti-rejection therapy.^[6] Maintenance immunosuppression continues for the life of the graft, and routine surveillance bronchoscopy monitors the anastomoses.^[6]

Anti-microbial prophylaxis is standard. For CMV, international practice is 6 to 12 months of valganciclovir or ganciclovir in CMV-seronegative recipients of seropositive donor organs, and 3 months in seropositive recipients. Pneumocystis jirovecii prophylaxis with co-trimoxazole and 3 to 12 months of antifungal prophylaxis (systemic and/or inhaled) are also used. Perioperative antibiotics target colonising organisms in donor and recipient.^[5] Acute cellular rejection of grade A2 or higher is treated with methylprednisolone 10 to 15 mg/kg (500 to 1,000 mg) daily for 3 days, then tapered with oral prednisolone; minimal (A1) rejection may be observed.^[5] Antibody-mediated rejection has no standard regimen and is treated with combinations of plasmapheresis, intravenous immunoglobulin, rituximab and eculizumab, with poor results.^[5]

Complications are common, multisystem and cumulative, and many derive from chronic immunosuppression rather than from the operation itself. Median survival has improved to 6.7 years in one large review, but CLAD and infection remain the leading late causes of death.^[5]

Primary graft dysfunction (PGD) is ischaemia-reperfusion injury of the graft, from mild oedema to severe hypoxaemia early after transplant. Risk factors include donor quality, size mismatch, prolonged ischaemic time, bypass time and blood loss. Treatment is supportive (lung-protective ventilation, inhaled nitric oxide), with ECMO for severe cases, and severe PGD raises the risk of early death and later chronic dysfunction.^[8][5]

Graft failure or rejection accounts for about 22.7% of deaths within the first year. Acute cellular rejection is commonest in the first 3 to 6 months and within the first 1 to 2 years, and is diagnosed by a fall in lung function above 10%, chest imaging and transbronchial biopsy showing perivascular lymphocytic infiltrates. Donor-specific antibodies and CMV infection are risk factors, and acute rejection predisposes to later CLAD.^[5]

CLAD is the umbrella term for significant, persistent allograft dysfunction not explained by other, reversible causes, occurring more than 3 months after transplant. It is defined by a sustained fall in FEV1 of at least 20% from the baseline (mean of the best two postoperative FEV1s at least 3 weeks apart). A smaller decline should still trigger investigation and action even before the 20% threshold is reached. A decline that persists 3 months after the first measurement and after treatment of reversible causes is "confirmed CLAD". Additional exclusion criteria include confounders (ageing, surgical or mechanical problems, airway stenosis, scarring, rejection that clears within 3 months).^[2]

The two main phenotypes are:

• BOS (bronchiolitis obliterans syndrome): FEV1/FVC under 0.7, TLC not under 90% of baseline, no opacities on HRCT.
• RAS (restrictive allograft syndrome): fall in FEV1 of 20% or more, TLC at or under 90% of baseline, with persistent opacities on chest imaging. RAS carried worse survival (about 1 year from diagnosis, versus 2.5 years for BOS) and is found in about 30% of patients with CLAD.^[2]

CLAD severity is staged by FEV1 as a percentage of baseline: stage 0 above 80%; stage 1, 66-80%; stage 2, 51-65%; stage 3, 35-50%; stage 4 under 35%. Isolated BOS is defined by the same FEV1 fall of 20% or more, airflow limitation (FEV1/FVC under 0.7) and absence of imaging opacities. Baseline lung allograft dysfunction (failure of baseline spirometry to normalise on population predicted values) is itself an independent predictor of mortality after transplant.^[2]

There are few treatment options. Sustained high-dose corticosteroids should be avoided (lack of efficacy, harm). Trials of macrolides (azithromycin for 8 weeks or more), conversion of cyclosporine to tacrolimus, and early anti-reflux surgery for documented reflux can help some patients. Total lymphoid irradiation, extracorporeal photopheresis (more useful in slowly progressive BOS) and retransplantation (for advanced, well-selected CLAD, particularly BOS rather than RAS) are reserved for advanced disease, and RAS has no formal treatment guidelines. The 1993 working formulation (Cooper), the 2014 ISHLT/ATS/ERS BOS guideline (Meyer et al.) and the 2019 ISHLT CLAD consensus (Verleden et al.) are the key guideline editions that shaped these criteria; the numbers here are taken from a 2020 review that reports them.^[2] The 2026 ESOT guideline on CLAD prevention and treatment conditionally supports considering montelukast in early-stage BOS, found the evidence for anti-thymocyte globulin, alemtuzumab and extracorporeal photopherasis inconclusive compared with standard care, and does not support antifibrotics in BOS (very low to low certainty).^[9]

Infection is a major cause of death after lung transplantation, accounting for many late deaths. Infections strike in predictable phases (donor-derived and nosocomial early; opportunistic infections after; community-acquired later), and airway anatomy is vulnerable because bronchial arteries are not revascularised and mucociliary clearance and cough are impaired.^[5]

• Bacterial pneumonia: up to 50% of all infections; Pseudomonas, Staphylococcus and multidrug-resistant organisms are prominent; bacterial transmission from donor to recipient occurs in 48-89% of transplants; incidence of infection of any kind is about 70% in the first year.^[5]
• Fungal infection: 3 to 19% in the first year, most commonly Aspergillus (44%) and Candida (23%). Invasive fungal infection causes about 40% of deaths when it disseminates and accounts for about 80% of deaths with a disseminated IFI in some series.^[5]
• Viral: CMV up to the first 6 months; oral ribavirin is used for paramyxoviral infections. Post-transplant lymphoproliferative disorder, EBV-related, reaches up to 30% in lung recipients.^[5]
• Mycobacterial infection occurs after transplant in roughly 4% in some series (6.5% in a South Korean cohort, mostly Mycobacterium abscessus), without a clear increase in mortality.^[5]
• Endothelial hyperammonaemia, disseminated Nocardia infection, and COVID-19 (up to 40% mortality in transplant recipients) are noteworthy special problems.^[5]

After surgery, airway complications are the commonest complication: sloughing, exophytic granulation, anastomotic dehiscence, bronchial stenosis, vanishing airway syndrome and tracheobronchomalacia. Airways heal slowly because the bronchus is not revascularised, which is why the donor bronchus is cut short and revascularisation takes 2 to 4 weeks. Interventions range from balloon dilation and stenting to reoperation.^[8][5]

Chronic immunosuppression produces a familiar list, quantified in one large review.^[5]

• Cardiovascular: hypertension in 50% by 1 year and 80% by 5 years; atrial arrhythmias in 25 to 45%; target control below 130/80 mmHg with calcium-channel blockers favoured (avoid angiotensin-converting enzyme inhibitors and angiotensin receptor blockers because of renal risk); hyperlipidaemia in 27% by 1 year and 58% by 5 years, treated with statins (watch interactions and rhabdomyolysis). ^[5]
• Endocrine: post-transplant diabetes in 20 to 40% of recipients by 1 year (and 33 to 60% by 5 years); insulin in the early high-dose phase, with lifestyle measures thereafter. ^[5]
• Renal: acute kidney injury in 50 to 70% of recipients (pooled estimate about 53%); chronic kidney disease in 34% by 1 year and 53% by 5 years in one review (27% and 58% in its own text, and 15 to 86% across reported series, depending on definition), driven by calcineurin inhibitors and hypoperfusion. ^[5]
• Gastrointestinal: gastro-oesophageal reflux in 65%, gastroparesis in 24%; fundoplication improves outcomes in BOS. Severe ileus or colonic perforation can be fatal early. ^[5]
• Haematological: cytopenias, thrombocytopenia, venous thromboembolism in 10 to 60% of recipients (5 to 45% in recent series), pulmonary embolism in up to 15% (7 to 16% in recent series). Prophylaxis is essential. ^[5]
• Neurological: delirium, seizures (23%), stroke (5%), posterior reversible encephalopathy syndrome (0.5 to 5%), tremor and cognitive disturbance; neurotoxicity from immunosuppressive drugs. ^[5]
• Malignancy: skin cancer (1.9% at 1 year, 14.6% at 5 years), post-transplant lymphoproliferative disorder (0.9% at 1 year, 1.4% at 5 years), and others. ^[5]
• Musculoskeletal: osteoporosis (32 to 54%) with fractures in 6 to 18% in the first year; bisphosphonates, calcium/vitamin D and activity. ^[5]
• Psychiatric: delirium, mood disorder and anxiety in 30%, post-traumatic stress disorder. ^[5]

Venous congestion from a stenosed left atrial cuff, catastrophic early infections and adult respiratory distress syndrome are other early dangers; airway anastomotic dehiscence can follow fungal tracheobronchitis.

Palliative care is not the same as giving up. The 2023 ERS clinical practice guideline defines palliative care for COPD or ILD as "a holistic and multidisciplinary, person-centred approach aiming to control symptoms, and improve quality of life of people with serious health-related suffering because of COPD or ILD, and to support their informal caregivers".^[3] It is appropriate at any stage of serious illness, integrated with curative or disease-modifying treatment, and distinct from hospice care (care near the end of life).^[4]

When to start: the ERS guideline, a 2023 guideline, suggests a palliative care approach when people with COPD or ILD and their caregivers have physical, psychological, social or spiritual/existential unmet needs. Needs should be found by asking, but disease-severity markers and health-care use can help identify those likely to have them. The ATS policy statement (2022) explains that primary (generalist) palliative care delivered by pulmonary clinicians concurrent with disease treatment is the starting point, escalating to secondary (specialist) services when needs exceed frontline skill.^[3][4]

What the evidence supports (mostly conditional recommendations based on very low to low quality evidence) is to: integrate palliative care into routine care, explicitly recognising disease management and palliative care as complementary; provide accessible multidisciplinary holistic assessment of physical, psychological, social and spiritual/existential needs; embed a system within the extended multidisciplinary team so that people with persistent unmet palliative needs can reach specialist support; foster continuity with trusted clinicians; and offer advance care planning in accordance with individual needs and values, revised periodically.^[3] Advance care planning should be offered to people with COPD and to people with ILD.^[3] Recommendations should be reconsidered as new evidence becomes available.^[3]

Two practical consequences follow for chronic lung disease, including patients destined for transplant evaluation. First, most people with COPD or ILD do not need ongoing specialist palliative care, but needs must be sought systematically so expertise is involved when appropriate.^[3] Second, the ISHLT 2021 consensus already asks for simultaneous palliative care referral at transplant evaluation, aligning transplant and palliative teams before decisions are forced by crisis.^[1]

For symptoms, the ATS document reminds clinicians that dyspnoea, cough, pain, fatigue, sleep disturbance and psychological and spiritual distress, plus caregiver strain, should be assessed at every encounter, using validated tools, because symptoms are often missed or underreported.^[4] Breathlessness in particular deserves attention throughout: it drives emergency visits, limits daily life and is often under-treated.

• Children: cystic fibrosis is the leading indication in children 6 to 17 years and idiopathic pulmonary arterial hypertension in those 1 to 5 years; younger children face long waits for appropriately sized organs, so refer early. CF referral uses the same FEV1 thresholds (below 50% predicted and rapidly declining or markers of shortened survival; below 40% predicted), with listing below 30% predicted. PAH children are stratified by risk, with referral in intermediate or high risk despite triple therapy and listing in the high-risk category without improvement. Alveolar capillary dysplasia, refractory pulmonary vein stenosis and pulmonary veno-occlusive disease need urgent evaluation.^[1]
• Older adults: age alone is not a bar, but age over 70 carries substantially higher risk and worse long-term survival; individual selection matters.
• Cystic fibrosis and bronchiectasis: multi-organ implications (sinus, nutrition, resistant infection). Burkholderia cenocepacia confers worse post-transplant survival.
• Multi-organ transplantation: heart-lung for Eisenmenger syndrome and severe PAH (about 35% of heart-lung indications historically); simultaneous lung-liver and lung-kidney for advanced combined failure; retransplantation (mostly for CLAD) carries lower peak function and higher postoperative mortality. ^[6]
• Cardiac surgery and lung transplant together for coronary disease, where medically appropriate.

• A simplified assessment (spirometry, DLCO, 6-minute walk, resting and exertional oximetry, echocardiography) can identify most candidates; complex immunological and imaging work-up may be centralised.
• Where transplant is unavailable locally, focus on oxygen, pulmonary rehabilitation, nutrition, infection control and palliative care.
• End-of-life care, symptom relief (opioids for breathlessness titrated carefully), and advance care planning are low-cost and high-value, and can follow the needs-based approach of the ERS 2023 guideline even with minimal specialist palliative services.^[3]

• Lung transplantation is the definitive treatment for carefully selected end-stage lung disease, but it is a scarce resource and net survival benefit guides selection.^[1]
• General criteria: more than 50% risk of death within 2 years without transplant, and more than 80% chance of 5-year post-transplant survival from a general medical perspective.^[1]
• Refer early, before listing criteria are met; this protects prehabilitation, vaccination, optimisation and honest decision making.^[1]
• Disease-specific triggers (BODE, FVC/DLCO decline, FEV1 cut-offs, PAH risk scores) tell you when to act.^[7]
• Many contraindications are relative or risk factors that interact; refusal should be a team decision, not a unilateral gate, with parallel palliative care referral at evaluation.^[1]
• Surgery replaces lungs sequentially: bronchus, then pulmonary artery, then left atrial cuff, with controlled 10-minute reperfusion and lung-protective ventilation.^[8]
• Complications include PGD, rejection, infection (especially CMV and Aspergillus), airway complications, and chronic drug-related disease across many systems.^[5]
• CLAD affects about half of recipients by 5 years; diagnose at a 20% FEV1 fall from baseline, stage from 0 to 4, distinguish BOS from RAS.^[2]
• Palliative care should be needs-based, offered early and together with disease treatment, for people with COPD or ILD.^[3][4]

Chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis and interstitial lung disease; cystic fibrosis; pulmonary arterial hypertension; bronchiolitis obliterans syndrome and restrictive allograft syndrome (chronic lung allograft dysfunction); primary graft dysfunction; extracorporeal membrane oxygenation; palliative care in serious respiratory illness; pulmonary rehabilitation; lung volume reduction surgery; respiratory failure; mechanical ventilation.