In an adult who had a double lung transplant five years ago and now has a chronic cough and scratchy throat, what evaluation and management should be undertaken?

Chronic Cough and Scratchy Throat in Double Lung Transplant Recipient at 5 Years

This patient requires urgent evaluation for bronchiolitis obliterans syndrome (BOS) and infectious complications, as both are leading causes of morbidity and mortality beyond 5 years post-transplant, with BOS affecting over 50% of recipients at this timepoint. 1

Immediate Diagnostic Evaluation

Pulmonary Function Testing

• Obtain spirometry immediately to compare FEV1 to baseline post-transplant values 1
• BOS is defined as a persistent decline in FEV1 to ≤80% of baseline post-transplant FEV1 present for minimum 3 weeks, in the absence of other confounding conditions 1
• Even a 10-20% decline in FEV1 or ≥25% decline in FEF25-75% (BOS Grade 0-p) warrants close monitoring as "potential BOS" 1

Imaging Studies

• Perform high-resolution CT chest with contrast to characterize any parenchymal abnormalities and assess for air trapping or mosaic attenuation patterns suggestive of BOS 2, 3
• CT can identify post-surgical complications (bronchial stenosis, anastomotic issues) and infectious processes that may present with similar symptoms 3

Bronchoscopy with Comprehensive Sampling

• Bronchoscopy with bronchoalveolar lavage (BAL) is mandatory to exclude infection and assess for rejection 2
• BAL should include: bacterial cultures, fungal cultures and galactomannan, viral studies (PCR panel for community-acquired respiratory viruses), and cytology 2
• Transbronchial biopsy should be performed to evaluate for acute cellular rejection, lymphocytic bronchiolitis, or obliterative bronchiolitis 1

Serologic Testing

• Obtain serum galactomannan and beta-D-glucan for fungal infection screening 2
• Check CMV viral load, as CMV pneumonitis is a recognized risk factor for BOS 1

Critical Differential Diagnoses at 5 Years Post-Transplant

Bronchiolitis Obliterans Syndrome (Most Likely)

• BOS affects >50% of recipients surviving beyond 5 years and is the leading cause of death after 1 year post-transplant 1
• Symptoms are often nonspecific (cough, dyspnea, scratchy throat) before spirometric decline becomes evident 1
• Multiple risk factors include: prior acute rejection, lymphocytic bronchiolitis, CMV pneumonitis, community-acquired respiratory virus infections, Pseudomonas colonization, and gastroesophageal reflux 1

Infectious Complications

• At 5 years post-transplant, bacterial (especially Pseudomonas and Staphylococcus), fungal (Aspergillus), and viral (community respiratory viruses) infections remain significant threats 4, 5
• Community-acquired respiratory viruses can trigger acute rejection and accelerate BOS development 6, 7
• Aspergillus colonization or infection is particularly concerning as a risk factor for complications 2

Coexisting Infection and Rejection

• Infection and rejection frequently coexist in the allograft and must both be evaluated simultaneously 2

Management Algorithm

If BOS is Confirmed or Suspected

First-Line Therapy:

• Initiate azithromycin 250 mg daily for 5 days, then 250 mg three times weekly for minimum 3 months 8
• If currently on cyclosporine, switch to tacrolimus with target trough levels 5-15 ng/mL 8

Address Underlying Risk Factors:

• Aggressively treat any identified infections, as infections exacerbate BOS and worsen outcomes 8, 5
• Evaluate for gastroesophageal reflux disease; if confirmed, consider surgical fundoplication to reduce aspiration risk and slow BOS progression 8

Avoid:

• Long-term high-dose corticosteroids (>30 mg/day prednisone) provide minimal benefit for BOS and increase adverse effects 8

Advanced Therapies if Progressive:

• Consider extracorporeal photopheresis (ECPP) or total lymphoid irradiation (TLI) for refractory cases 8
• Lung re-transplantation may be considered for end-stage BOS unresponsive to other therapies 8

If Infection is Identified

• Targeted antimicrobial therapy based on culture and sensitivity results 5
• For viral infections, particularly influenza, avoid corticosteroids as they increase mortality (OR 3.06) and superinfection risk 9
• For fungal infections (especially Aspergillus), initiate appropriate antifungal therapy promptly 2

Ongoing Monitoring

• Regular spirometry monitoring is essential to track disease progression and treatment response 8
• Continue surveillance bronchoscopy as clinically indicated to detect occult infections in this high-risk period 2
• Serial high-resolution CT imaging to assess disease progression 8, 3

Critical Pitfalls to Avoid

• Do not attribute symptoms solely to "post-transplant changes" without thorough evaluation - numerous reversible causes of delayed graft dysfunction must be excluded before diagnosing BOS 1
• Do not delay bronchoscopy - infection and rejection can coexist and both require specific treatment 2
• Do not overlook community-acquired respiratory viruses - these are increasingly recognized as triggers for acute rejection and BOS development 6, 7
• Do not assume stable immunosuppression is adequate - at 5 years, prophylactic antimicrobial coverage may be waning while immunosuppression remains substantial, creating a critical window for opportunistic infections 2