What is the treatment for pleuro-pulmonary fibroelastosis?

Treatment for Pleuropulmonary Fibroelastosis (PPFE)

There is currently no proven effective pharmacological therapy for pleuropulmonary fibroelastosis, with lung transplantation being the best therapeutic option for eligible patients with progressive disease.

Disease Overview

Pleuropulmonary fibroelastosis (PPFE) is a rare form of idiopathic interstitial pneumonia characterized by:

• Upper lobe predominant fibrosis involving the visceral pleura and subpleural lung parenchyma
• Distinctive fibroelastic changes in the lung tissue
• Progressive nature with variable disease course
• Typical radiological findings on HRCT showing pleural-based opacities and reticular pattern with parenchymal distortion in upper lobes

Treatment Approach

First-line Management

1. Immunosuppressive Therapy:

   • Corticosteroids (prednisone) starting at 0.5 mg/kg lean body weight per day orally for 4 weeks, then 0.25 mg/kg for 8 weeks, followed by taper to 0.125 mg/kg daily or 0.25 mg/kg every other day 1
   • Combined with either:
     • Azathioprine (2-3 mg/kg lean body weight per day, maximum 150 mg/day) OR
     • Cyclophosphamide (2 mg/kg lean body weight per day, maximum 150 mg/day) 1

2. Treatment Duration and Monitoring:

   • Continue combined therapy for at least 6 months before assessing response
   • Perform objective assessments at 6 months, 12 months, and 18 months including:
     • Dyspnea assessment using established clinical scales
     • Pulmonary function tests (lung volumes, DLCO)
     • Arterial blood gases
     • HRCT scans 1

3. Response Assessment:

   • If improved or stable: continue therapy
   • If worsening: consider changing therapy or referral for lung transplantation evaluation 1

Special Considerations

• Despite treatment with immunosuppressive agents (including pirfenidone), PPFE has been observed to progress in many patients 2
• Recurrent pneumothorax is a common complication (reported in 88% of patients in one series) and may require specific management 2
• Patients often develop hypercapnic respiratory failure as the disease progresses 2

Lung Transplantation

• Lung transplantation should be considered early in the disease course for eligible patients, as it represents the only definitive treatment option 3, 4
• Early referral is important as the disease can progress rapidly in some patients

Monitoring and Supportive Care

1. Regular Pulmonary Function Monitoring:

   • Monitor for characteristic physiological changes:
     • Restrictive pattern with reduced FVC (median 55.4% predicted)
     • Preserved or increased residual volume (RV/TLC ratio median 143.6% predicted)
     • Development of hypercapnia 2

2. Nutritional Support:

   • Monitor and address weight loss, which is common and contributes to platythorax (flattened thoracic cage) 4

3. Pneumothorax Management:

   • Be vigilant for recurrent pneumothorax, which is a frequent complication 2

Prognosis

• Disease course is variable but generally progressive
• Poorer prognosis when PPFE coexists with other interstitial lung diseases 3
• Respiratory failure is the most common cause of death, particularly hypercapnic respiratory failure 2

Pitfalls and Caveats

• PPFE may be associated with connective tissue diseases, and underlying conditions should be identified and treated 5
• Diagnosis requires characteristic HRCT findings, and confirmation by lung biopsy when feasible
• Acetylcysteine has been tried but has not shown effectiveness in preventing disease progression 6
• The disease can be mistaken for other interstitial lung diseases, particularly when lower lobe involvement is present

Despite the lack of proven effective medical therapy, early diagnosis and appropriate management of complications are crucial for optimizing patient outcomes while lung transplantation remains the definitive treatment option for eligible patients with progressive disease.