How should I evaluate and manage a patient with a persistent dry cough and scratchy throat five years after lung transplantation?

Evaluation and Management of Persistent Dry Cough and Scratchy Throat 5 Years Post-Lung Transplant

This patient requires urgent evaluation for chronic lung allograft dysfunction (CLAD), as persistent cough 5 years post-transplant is a cardinal symptom of bronchiolitis obliterans syndrome (BOS), the most common phenotype of CLAD, which carries significant mortality risk. 1, 2, 3

Immediate Diagnostic Workup

Pulmonary Function Testing

• Obtain spirometry immediately to assess for obstructive physiology (declining FEV1), which defines BOS when FEV1 falls ≥20% from baseline without other identifiable causes 2, 3, 4
• Compare current FEV1 to the patient's post-transplant baseline (average of two best measurements taken 3+ weeks apart) 3
• A persistent decline in FEV1 ≥20% from baseline is diagnostic of CLAD grade 1 or higher 3, 4

High-Resolution CT Chest

• CT scan is essential to differentiate CLAD phenotypes and exclude other causes of cough 5, 3
• Look for air trapping on expiratory images (suggests BOS), bronchial wall thickening, or ground-glass opacities with peripheral distribution (suggests restrictive allograft syndrome) 5, 3
• CT helps exclude infections, anastomotic complications, or malignancy (post-transplant lymphoproliferative disease) 5

Bronchoscopy with Bronchoalveolar Lavage

• Perform bronchoscopy to exclude treatable causes including acute cellular rejection, antibody-mediated rejection, and infections 5, 3
• Send BAL for bacterial, fungal, viral cultures, and specifically screen for non-tuberculous mycobacteria (NTM) before considering macrolide therapy 6, 7, 8
• Transbronchial biopsies can identify acute rejection or infection patterns 5, 3

Additional Laboratory Assessment

• Obtain donor-specific antibodies (DSA) testing to assess for antibody-mediated rejection 9
• Check for gastroesophageal reflux disease (GERD), as this is a common alloimmune-independent contributor to CLAD 2, 9

Management Strategy

If CLAD/BOS is Confirmed

Initiate azithromycin 250mg three times weekly as first-line therapy for neutrophilic reversible allograft dysfunction, a BOS subtype that responds to macrolides 1, 7, 2

• This regimen reduces exacerbation rates and may stabilize lung function decline 1, 7, 8
• Mandatory pre-treatment ECG to exclude QTc >450ms (men) or >470ms (women), which is an absolute contraindication 1, 7, 8
• Baseline liver function tests required, with repeat monitoring at 1 month then every 6 months 7, 8
• Assess response at 6 months using objective measures (FEV1 trajectory, exacerbation frequency, quality of life scores) 7, 8

Optimize Immunosuppression

• Coordinate with transplant pulmonology to adjust maintenance immunosuppression regimen 2, 9
• Consider augmented immunosuppression if acute rejection is identified on biopsy 9

Symptomatic Management of Cough

Prescribe opioid-based antitussives (codeine or morphine) for persistent troublesome cough that impairs quality of life 6

• Opioids are the most effective cough suppressants when no treatable cause is identified 6
• Benzonatate can be considered as an alternative if opioids are ineffective 6

Consider inhaled corticosteroids if there is evidence of airway inflammation on bronchoscopy 6

• May help reduce cough related to inflammatory processes 6

Address Gastroesophageal Reflux

• Initiate proton pump inhibitor therapy, as GERD is both a contributor to CLAD development and a cause of chronic cough 2, 9

Critical Pitfalls to Avoid

• Never dismiss chronic cough in lung transplant recipients as benign - it may herald life-threatening CLAD, which has 5-year survival rates of only 40-60% once established 6, 2
• Do not start azithromycin without excluding NTM infection, as macrolide monotherapy for NTM is contraindicated and promotes resistance 6, 7, 8
• Do not delay transplant team notification - patients with severe CLAD may require re-transplantation evaluation, and waiting list mortality for bronchiectasis/CLAD patients approaches 60% at 2 years 6
• Avoid empiric treatment without bronchoscopy - infections (bacterial, viral, fungal) are common 5 years post-transplant due to chronic immunosuppression and can mimic CLAD symptoms 6, 5

Infection Risk Considerations

At 5 years post-transplant, this patient remains at elevated risk for opportunistic infections including:

• Cytomegalovirus, Aspergillus species, and NTM 6, 5
• Bacterial pneumonias with resistant organisms 6
• Any infection in the setting of CLAD poses life-threatening risk and requires aggressive treatment 1

Prognosis and Follow-up

• Early-onset BOS (within 2 years) has worse prognosis than late-onset, but all CLAD phenotypes carry significant mortality 2
• Restrictive allograft syndrome (RAS) has poorer survival than BOS 2, 3
• Close monitoring every 3-6 months with spirometry and symptom assessment is essential 7, 4
• Consider palliative care consultation early given the significant psychological, physical, and social impacts of CLAD 2