Lung Transplantation · Reference for Medical Students

🫁 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)

Disease	Key Referral Criteria	Listing Criteria (Examples)
COPD	Progressive disease despite maximal therapy, not candidate for LVRS. BODE index 5‑6.	FEV₁ <20% predicted + hypercapnia (PaCO₂ >50) or cor pulmonale. Frequent exacerbations despite triple therapy.
ILD / IPF	Histopathologic or radiographic UIP, fibrotic NSIP. Progressive dyspnea, ↓ FVC, ↓ DLCO.	FVC <80% predicted, DLCO <40%, desaturation on 6MWT, honeycombing on HRCT. Earlier referral critical due to high mortality.
Cystic Fibrosis / Bronchiectasis	FEV₁ <30% predicted, or rapidly declining FEV₁ despite CFTR modulators.	FEV₁ <25%, frequent exacerbations requiring ICU, massive hemoptysis, pneumothorax, or BMI <18.
Pulmonary Arterial Hypertension (PAH)	WHO Group 1 PAH on maximal medical therapy (triple therapy including parenteral prostacyclin).	Persistent NYHA III‑IV symptoms, 6MWD <350m, elevated RAP >15 mmHg, low CI <2 L/min/m², or evidence of RV failure.

📈 LAS Score (Lung Allocation Score): Used in the U.S. to prioritize candidates on the waitlist. Ranges 0‑100, based on medical urgency (predicted 1‑year survival without transplant) minus expected post‑transplant survival. Higher LAS = higher priority.

3. Absolute & Relative Contraindications (ISHLT 2021)

Absolute Contraindications

Active malignancy within 2‑5 years (except non‑melanoma skin cancer)
Untreatable significant dysfunction of another major organ (heart, liver, kidney) unless combined transplant planned
Uncorrected bleeding diathesis
Active, untreated infection (including TB, HIV with CD4 <200)
Substance abuse / addiction (including tobacco, alcohol, cannabis) within 6 months
Severe chest wall or spinal deformity expected to cause restriction after transplant
Non‑adherence to medical therapy or lack of social support
BMI >35 or <16

Relative Contraindications

Age >75 (SLT) or >65 (BLT) — varies by center
BMI 30‑35 or 16‑17
Severe osteoporosis
Extensive prior thoracic surgery, pleurodesis
Chronic infection with highly resistant organisms (e.g., Burkholderia cenocepacia, Mycobacterium abscessus)
Severe esophageal dysmotility / GERD
Psychiatric or psychosocial issues that may impair adherence

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

Procedure	Indications	Advantages	Disadvantages
Single Lung Transplant (SLT)	COPD, IPF (in older patients), PAH (rarely)	Shorter surgery, one lung remains native, maximizes donor organ use	Native lung can cause complications (hyperinflation in COPD, infection, malignancy); lower long‑term survival than BLT
Bilateral Lung Transplant (BLT)	Cystic Fibrosis / bronchiectasis (mandatory), younger IPF patients, PAH	Better long‑term survival, fewer complications from native lung, better functional outcomes	Longer surgery, higher perioperative risk, requires two donor lungs
Heart‑Lung Transplant	Complex congenital heart disease with Eisenmenger syndrome, severe left heart failure + lung disease	Treats both cardiac and pulmonary disease simultaneously	Highest mortality, limited donor availability, complex surgery

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

Time Period	Common Pathogens	Prophylaxis / Monitoring
Early (<1 month)	Bacterial (Pseudomonas, S. aureus, Enterobacteriaceae), donor‑derived infections	Perioperative broad‑spectrum antibiotics tailored to donor cultures
Intermediate (1‑6 months)	CMV (pneumonitis, colitis), EBV (PTLD), fungal (Aspergillus), PJP, Nocardia	Valganciclovir (CMV), TMP‑SMX (PJP), voriconazole or inhaled amphotericin (antifungal)
Late (>6 months)	Community‑acquired respiratory viruses (influenza, RSV, SARS‑CoV‑2, parainfluenza), bacterial pneumonia, NTM	Vaccinations (inactivated only), early antiviral therapy for respiratory viruses

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)

Class	Drug	Mechanism	Major Adverse Effects
Calcineurin Inhibitor (CNI)	Tacrolimus (preferred) Cyclosporine	Inhibits IL‑2 transcription	Nephrotoxicity, hypertension, tremor, diabetes, neurotoxicity
Antimetabolite	Mycophenolate Mofetil (MMF) Azathioprine	Inhibits purine synthesis (lymphocyte proliferation)	GI upset, myelosuppression, teratogenicity
Corticosteroid	Prednisone	Broad anti‑inflammatory, inhibits cytokine production	Weight gain, osteoporosis, diabetes, hypertension, cataracts
mTOR Inhibitor	Sirolimus, Everolimus	Inhibits cell cycle progression	Delayed wound healing, hyperlipidemia, proteinuria, pneumonitis

⚠️ Avoid mTOR inhibitors in the early post‑operative period due to impaired bronchial anastomotic healing. Usually introduced >3‑6 months post‑transplant.

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

Time Point	Survival (ISHLT Registry)	Major Causes of Death
1 Year	~85‑90%	Primary graft dysfunction, infection, technical complications
3 Years	~70‑75%	Infection, acute rejection
5 Years	~60%	Chronic lung allograft dysfunction (CLAD), infection, malignancy
10 Years	~30‑35%	CLAD, malignancy, cardiovascular disease

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

Indications

COPD (FEV₁ <20%, hypercapnia)
ILD/IPF (FVC <80%, DLCO <40%)
CF (FEV₁ <30%, frequent exacerbations)
PAH (refractory to triple therapy)

Absolute Contraindications

Active malignancy
Untreatable major organ dysfunction
Active infection
Substance abuse
BMI >35 or <16
Non‑adherence

💡 CLAD Mnemonic: "BOS vs. RAS"
BOS: Obstructive, Bronchiolitis obliterans, Air trapping, Azithromycin may help.
RAS: Restrictive, Rapid decline, Refractory to treatment, Really bad prognosis.

🫁 Lung Transplantation Reference · High‑yield for medical students, pulmonary rotations, and transplant electives.
Covers indications, contraindications, candidate selection, donor criteria, surgical types, post‑transplant complications, immunosuppression, and long‑term outcomes.