🫁 Lung Transplantation A Comprehensive Reference for Medical Students · Candidate Selection to Long‑Term Management

1. Overview & Epidemiology

• Lung transplantation is a life‑saving treatment for select patients with end‑stage, non‑malignant lung disease refractory to maximal medical therapy.
• Annual volume: ~4,500 worldwide (ISHLT Registry). Median survival ~6‑7 years, but improving.
• Most common indications: Interstitial Lung Disease (ILD, including IPF) ~35%, COPD ~30%, Cystic Fibrosis / Bronchiectasis ~15%, Pulmonary Arterial Hypertension (PAH) ~5%.
• Procedure types: Single lung transplant (SLT), bilateral lung transplant (BLT), heart‑lung transplant, lobar transplant (living donor or split deceased donor).

2. Indications for Lung Transplantation

General Principle Refer when chronic lung disease is advanced, progressive, and associated with high (>50%) risk of death within 2 years without transplant, AND the patient has no absolute contraindications.

Disease‑Specific Referral Criteria (ISHLT 2021)

3. Absolute & Relative Contraindications (ISHLT 2021)

4. Donor Selection & Organ Allocation

Ideal Donor Criteria

• Age <55 years, no significant smoking history (<20 pack‑years), normal CXR, clear bronchoscopy.
• ABO compatible. Human leukocyte antigen (HLA) matching not routinely performed (unlike kidney).
• PaO₂ >300 mmHg on FiO₂ 1.0, PEEP 5 cm H₂O.

Extended Criteria Donors (ECD)

• Increasingly used to expand donor pool: age >55, smoking history 20‑40 pack‑years, abnormal CXR (contusion, infiltrate), positive cultures, donation after circulatory death (DCD).
• Ex‑Vivo Lung Perfusion (EVLP): Allows assessment and reconditioning of marginal donor lungs before transplant.

Allocation in the U.S. (OPTN / LAS System)

• Organs offered first to candidates within 250 nautical miles of donor hospital with highest LAS.
• Blood type O candidates have longer wait times.
• Median wait time: 2‑4 months for high LAS; >12 months for lower LAS.

5. Surgical Procedure Types

6. Post‑Transplant Complications

Primary Graft Dysfunction (PGD)

• Form of acute lung injury within 72 hours post‑transplant. Due to ischemia‑reperfusion injury, surgical trauma, inflammation.
• Characterized by hypoxemia and diffuse alveolar infiltrates on CXR, without other cause (cardiogenic edema, rejection, infection).
• Severity graded by PaO₂/FiO₂ ratio and CXR infiltrates (Grade 0‑3).
• Management: Supportive (lung‑protective ventilation, diuresis, inhaled nitric oxide, ECMO if severe).

Acute Cellular Rejection (ACR)

• Most common in first 6‑12 months. Lymphocytic infiltration around vessels and airways.
• Often asymptomatic or subtle dyspnea, cough, low‑grade fever, ↓ spirometry (FEV₁).
• Diagnosis: Surveillance transbronchial biopsies (TBBx) + BAL to rule out infection. ISHLT grading: A0 (none) to A4 (severe).
• Treatment: Pulse IV methylprednisolone for A2 or higher; augmented maintenance immunosuppression.

Antibody‑Mediated Rejection (AMR)

• Less common but recognized. Donor‑specific antibodies (DSA) against HLA → complement activation, endothelial injury.
• Diagnosis: C4d deposition on biopsy, circulating DSA, histologic features (capillaritis, arteritis).
• Treatment: Plasmapheresis, IVIG, rituximab, bortezomib.

Chronic Lung Allograft Dysfunction (CLAD)

• Leading cause of late mortality after lung transplant. Defined as persistent ≥20% decline in FEV₁ from baseline without other cause.
• Two main phenotypes:
  • Bronchiolitis Obliterans Syndrome (BOS): Obstructive physiology (↓ FEV₁/FVC). Air trapping on CT. Histology: obliterative bronchiolitis (irreversible fibroproliferative narrowing of small airways).
  • Restrictive Allograft Syndrome (RAS): Restrictive physiology (↓ FVC and TLC). Persistent pleuroparenchymal opacities on CT. Worse prognosis than BOS.
• Risk factors: Recurrent ACR, AMR, GERD / aspiration, infections (CMV, community‑acquired viral), air pollution.
• Treatment: Limited. Azithromycin (for BOS), augmented immunosuppression, photopheresis, re‑transplantation (selected cases).

Infectious Complications

7. Immunosuppression Regimens

Induction Therapy

• Used in ~50‑70% of centers to reduce early rejection.
• Agents: Basiliximab (IL‑2 receptor antagonist), Alemtuzumab (anti‑CD52), or Antithymocyte globulin (ATG).

Maintenance Immunosuppression (Triple Therapy)

8. Long‑Term Surveillance & Preventive Care

• Pulmonary Function Tests (PFTs): Home spirometry daily or weekly. In‑lab PFTs at each clinic visit. >10‑20% drop in FEV₁ triggers evaluation (bronchoscopy with BAL and TBBx).
• Surveillance Bronchoscopy: Varies by center; often at 1, 3, 6, 12 months, then annually or when clinically indicated.
• Donor‑Specific Antibodies (DSA): Monitored periodically (every 3‑6 months) to detect early AMR.
• Cancer Screening: Increased risk of skin cancer (squamous cell), post‑transplant lymphoproliferative disorder (PTLD), lung cancer (especially in single lung recipients).
• Vaccinations: Inactivated vaccines only (influenza, pneumococcal, COVID‑19, RSV, shingles [RZV]). Avoid live vaccines.
• Management of Comorbidities: Hypertension, diabetes, osteoporosis, renal dysfunction (common due to CNI toxicity).

9. Outcomes & Prognosis

• Best survival: Bilateral lung transplant for CF, younger recipients, transplant at high‑volume centers.
• Worst survival: Single lung transplant for IPF, older recipients, re‑transplantation.
• Quality of Life: Dramatic improvement in functional status, dyspnea, and quality of life, though many patients face ongoing medical complexity.

10. Quick Reference: Lung Transplant Pearls