What is the recommended post‑lung‑transplant care protocol for an adult recipient, including induction and maintenance immunosuppression, infection prophylaxis, laboratory and pulmonary function monitoring, surveillance bronchoscopy schedule, rejection treatment, chronic complication management, and lifestyle recommendations?

Post-Lung Transplant Care Protocol

Immunosuppression

Induction Therapy

Induction immunosuppression should be initiated in the intensive care unit immediately following lung transplantation to prevent early acute rejection. 1

Maintenance Immunosuppression (Triple Therapy Standard)

Tacrolimus is the preferred calcineurin inhibitor for maintenance immunosuppression in lung transplant recipients, with target therapeutic trough blood levels of 5-15 ng/mL once steady state is achieved. 2

• Therapeutic drug monitoring of tacrolimus trough concentrations is mandatory to prevent toxicity. 2
• Monitor blood pressure, glucose, and renal function (serum creatinine) regularly in all patients on calcineurin inhibitors. 3

Mycophenolic acid (mycophenolate mofetil or mycophenolate sodium) is the standard antiproliferative agent. 2, 4

• If significant gastrointestinal intolerance (diarrhea) develops, temporarily interrupt or reduce the dose. 2
• If progressive multifocal leukoencephalopathy is suspected, immediately discontinue mycophenolic acid. 2

Corticosteroids (prednisone) are maintained long-term but avoid doses >30 mg/day chronically. 2, 5

Alternative Agents and Switches

For patients developing bronchiolitis obliterans syndrome (BOS) while on cyclosporine, switch to tacrolimus to mitigate lung function decline. 2, 5

mTOR inhibitors (sirolimus, everolimus) may be considered as alternatives but require specific precautions: 2

• Contraindicated in the early postoperative period due to increased risk of airway dehiscence. 2
• Avoid in patients with elevated fasting triglycerides or monitor closely if used. 2
• Regular measurement of drug concentrations, lipid profiles (cholesterol and triglycerides), renal function, and blood pressure is necessary. 2
• Evaluate for sirolimus-induced pulmonary toxicity if new or worsening respiratory symptoms develop. 2

CBC with differential is required for all patients receiving drugs associated with bone marrow suppression. 3

Infection Prophylaxis

Prophylactic antibiotic regimens have markedly reduced infections such as Pneumocystis jiroveci pneumonia and cytomegalovirus infection and should be implemented in all lung transplant recipients. 3

• The specific antibiotic agent for prophylaxis depends on the clinical situation and local resistance patterns. 3
• Combination immunosuppressive therapy increases the risk for opportunistic infections, requiring vigilant monitoring. 2

For patients with latent tuberculosis, active prophylactic treatment following published guidelines before or during immunosuppression is recommended. 3

Aggressive treatment of any coexisting infections is essential, as infections can exacerbate BOS and worsen outcomes. 5

Monitoring and Surveillance

Laboratory Monitoring

• Tacrolimus trough levels: Target 5-15 ng/mL, measured regularly to maintain therapeutic range. 2
• Complete blood count with differential: Monitor for bone marrow suppression. 3
• Comprehensive metabolic panel: Assess renal function (creatinine), glucose, and electrolytes. 3, 2
• Lipid panel: Especially critical for patients on mTOR inhibitors. 2
• Blood pressure: Monitor for hypertension related to calcineurin inhibitors and mTOR inhibitors. 3, 2

Pulmonary Function Testing

Regular spirometry monitoring is essential to track disease progression, treatment response, and early detection of rejection or BOS. 5, 6

• Spirometry should be performed at scheduled intervals and whenever clinical deterioration is suspected. 5
• A sustained decline in FEV1 of ≥20% from baseline defines BOS stage 1. 3

Surveillance Bronchoscopy

Bronchoscopy is frequently used to evaluate lung function decline and detect rejection, though it has poor sensitivity for diagnosing obliterative bronchiolitis. 5

• The frequency of surveillance bronchoscopy varies by center but is typically performed at regular intervals during the first year and as clinically indicated thereafter. 1, 7

Imaging

High-resolution CT imaging can help assess disease progression in BOS, though findings of air trapping and mosaic attenuation patterns lack sensitivity and specificity. 5

Rejection Management

Acute Cellular Rejection

For non-minimal acute cellular rejection (Grade ≥A2) or lymphocytic bronchiolitis, augmented immunosuppression with systemic steroids is recommended, including intravenous methylprednisolone 1000 mg daily for 3 days. 2

• This approach prevents BOS development. 2
• Careful surveillance after treatment helps maintain graft function and facilitates identification of recurrent rejection. 7

Chronic Rejection (Bronchiolitis Obliterans Syndrome)

Azithromycin is recommended as first-line trial therapy for BOS, administered at 250 mg daily for 5 days, then 250 mg three times weekly for at least 3 months. 2, 5

For patients with BOS on cyclosporine, switch to tacrolimus with target trough levels of 5-15 ng/mL. 2, 5

Avoid long-term high-dose corticosteroids (>30 mg/day of prednisone) as they provide minimal benefit and increase risk of adverse effects. 2, 5

For patients with confirmed gastroesophageal reflux disease (GERD), surgical fundoplication should be considered to reduce the risk of further lung function deterioration. 5

For progressive BOS refractory to standard therapies, consider extracorporeal photopheresis (ECPP) or total lymphoid irradiation (TLI). 3, 5

Lung re-transplantation should be considered as a last resort for end-stage BOS refractory to all other therapies. 5

Chronic Complication Management

Non-Tuberculous Mycobacterial (NTM) Infection

The risk of developing NTM infection is increased in lung transplant recipients due to powerful immunosuppression, and can arise de novo or by resurgence of pre-transplant organisms. 3

• Treatment requires a complex regimen of intravenous and oral antibiotics, usually for a prolonged period, with careful monitoring for drug-drug interactions. 3
• Colonization with highly resistant mycobacteria is a relative contraindication to lung transplantation. 3

Malignancy Surveillance

Solid-organ transplant recipients exhibit elevated risk for malignancies, including gynecologic cancers, driven by chronic immunosuppression. 4

• Azathioprine use is linked to higher incidence of certain malignancies, particularly HPV-related. 4
• Calcineurin inhibitors show a dose-dependent relationship with secondary malignancies. 4
• If cancer is diagnosed, consider switching azathioprine to mycophenolate mofetil (MMF) or converting to an mTOR inhibitor (sirolimus), which has demonstrated activity against solid tumors. 4

Early Postoperative Management

Meticulous attention during the early postoperative period in the intensive care unit includes initiation of immunosuppression, implementation of anti-infective strategies, and stabilization of respiratory function. 1

Subsequent days and weeks focus on titration of immunosuppressive drugs, vigilant fluid management, early mobilization, and initiation of physiotherapy. 1, 8

Active patient education about self-monitoring and self-management strategies is essential for smooth transition to outpatient follow-up care. 1

Lifestyle and Rehabilitation

Pulmonary rehabilitation and early mobilization are crucial components for positive functional outcomes after lung transplantation. 8

• The acute inpatient rehabilitation unit offers an ideal setting for patients to receive therapies while allowing for monitoring and medical management. 8
• Improvements in surgical techniques and medical management have resulted in 1-year survivorship of 70-93%. 7

Key Pitfalls to Avoid

• Never attribute clinical deterioration solely to medication side effects without first excluding rejection, infection, or malignancy. 4
• Do not modify immunosuppression unilaterally without multidisciplinary input from transplant pulmonology, as this may precipitate acute rejection. 4
• Vaccination responses may be impaired in transplant recipients on immunosuppression. 2
• Drug-drug interactions are common and require careful review when adding new medications. 3