What is the management approach for Pleuro-Parenchymal Fibroelastosis (PPFE)?

Management of Pleuroparenchymal Fibroelastosis (PPFE)

Antifibrotic therapy with nintedanib should be considered for patients with PPFE showing progressive disease, as it may slow disease progression in this rare interstitial lung disease with poor prognosis. 1

Understanding PPFE

PPFE is a rare interstitial lung disease characterized by:

• Fibrosis involving the visceral pleura and subpleural lung parenchyma
• Upper lobe and subpleural predominance
• Dense fibroelastic changes with prominent elastosis of alveolar walls
• Unique radiological features on CT scan showing upper lobe pleural thickening and subjacent parenchymal fibrosis

PPFE can be idiopathic or associated with various conditions including:

• Telomerase-related gene mutations
• History of chemotherapy
• Stem cell transplantation
• Coexistence with other interstitial lung diseases (ILDs)

Diagnostic Approach

1. High-Resolution CT (HRCT) Imaging:

   • Look for characteristic dense subpleural consolidation
   • Upper lobe predominance with traction bronchiectasis
   • Architectural distortion and upper lobe volume loss 2
   • Follow-up HRCT is indicated when clinical suspicion of worsening fibrosis exists

2. Histopathological Confirmation (when feasible):

   • Elastotic fibrosis of pleura and subpleural lung parenchyma
   • Intraalveolar fibrosis
   • May show mild changes of PPFE or other patterns such as UIP 2

3. Clinical Features:

   • Progressive dyspnea
   • Significant reduction in body mass
   • Development of platythorax (flattened thoracic cage)
   • Pneumothorax is common 2

Disease Monitoring

1. Pulmonary Function Testing:

   • Monitor for restrictive ventilatory defect
   • Track FVC decline (>5% absolute decline within 1 year indicates disease progression) 2

2. Quantitative CT Assessment:

   • Computer-based quantitative CT can provide objective measure of progression
   • More reproducible than visual assessment 2

3. Clinical Monitoring:

   • Assess for worsening respiratory symptoms
   • Monitor for weight loss and nutritional status
   • Evaluate for development of pneumothorax

Treatment Approach

1. Antifibrotic Therapy:

   • Consider nintedanib for progressive disease
   • Small retrospective studies suggest it may slow disease progression 1
   • Pirfenidone may also be considered based on recommendations for progressive pulmonary fibrosis, though specific evidence for PPFE is limited 2

2. Supportive Care:

   • Oxygen therapy for hypoxemia
   • Pulmonary rehabilitation
   • Nutritional support for weight loss
   • Prompt management of pneumothorax if it occurs

3. Advanced Disease Management:

   • Lung transplantation remains the only definitive therapeutic option for advanced disease 3, 4
   • Early referral for transplant evaluation is recommended for appropriate candidates

Prognosis and Monitoring

• Disease progression occurs in approximately 60% of patients
• Mortality from disease occurs in about 40% of patients 2
• PPFE concomitant with other ILDs (especially UIP pattern) is associated with poorer prognosis 1
• Regular follow-up with pulmonary function tests and imaging is essential

Special Considerations

• PPFE has been identified in approximately 10% of patients with idiopathic pulmonary fibrosis, 11% of patients with systemic sclerosis-associated ILD, 6.5% of patients with rheumatoid arthritis-associated ILD, and 23% of patients with hypersensitivity pneumonitis 1
• Post-transplant PPFE (following stem cell transplantation) may have a particularly aggressive course 5
• Pneumothorax management requires special attention as it is a common complication

While PPFE remains a challenging disease with limited treatment options, early recognition, appropriate monitoring, and consideration of antifibrotic therapy in progressive cases may help improve outcomes for these patients.