Pleuroparenchymal Fibroelastosis

A rare fibrotic lung disease with fibrosis of the visceral pleura and the adjacent subpleural lung in the upper lobes, with elastosis of the alveolar walls; progressive restriction and recurrent pneumothorax.

• Idiopathic in most patients (aged 40 to 60 years, with a similar rate in men and women); secondary forms follow bone marrow or lung transplantation (chronic graft rejection), chemotherapy with alkylating agents (cyclophosphamide, busulfan, carmustine), recurrent respiratory infection, asbestos or other dust exposure, connective tissue disease and familial telomere disorders.
• Mechanism: injury to the subpleural lung with persistent fibroblast activity and elastin deposition; the upper lobe predominance may reflect mechanical stress and reduced perfusion.
• Frequency is very low (published experience is limited); it makes up about 1 to 5% of fibrotic interstitial lung disease in referral centres.

Progressive exertional dyspnoea, dry cough, weight loss, recurrent chest infections, and spontaneous pneumothorax or pneumomediastinum (up to 30 to 40%).

• Flattened anteroposterior chest (platythorax), reduced chest expansion, low body mass index, and finger clubbing only in a minority.
• Examination: reduced breath sounds in the upper zones, fine crackles are unusual.
• Differential diagnosis: idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, post-tuberculous scarring, sarcoidosis (fibrotic), ankylosing spondylitis apical fibrosis, silicosis, asbestosis, chronic aspergillosis, radiation fibrosis.
• Complications: respiratory failure, pneumothorax, secondary infection (non-tuberculous mycobacteria, aspergilloma), pulmonary hypertension, malnutrition, and death (progressive in more than half).

High-resolution CT (the main tool): upper lobe pleural thickening with dense subpleural consolidation or fibrosis, traction bronchiectasis, volume loss with elevated hila and fissures, usually with normal or less affected lower lobes (a late basal usual interstitial pneumonia pattern can coexist).

• Pulmonary function: reduced forced vital capacity, raised residual volume to total lung capacity ratio (more than 50% in many patients), reduced diffusing capacity, 6 minute walk with oximetry.
• Exclude secondary causes: occupational and drug history, infection (Xpert MTB/RIF, mycobacterial and fungal cultures), connective tissue disease serology (antinuclear antibody, rheumatoid factor, anti-cyclic citrullinated peptide, myositis panel), telomere or genetic testing in familial disease.
• Multidisciplinary discussion: biopsy is high risk (pneumothorax, prolonged air leak) and rarely needed when CT is typical; if needed, use cryobiopsy or video-assisted surgery with care.

No therapy is proven to stop progression; discuss prognosis early and plan supportive and palliative care.

• Antifibrotic therapy (evidence limited, extrapolated from other fibrosing lung disease): nintedanib 150 mg twice daily with food (100 mg twice daily with mild hepatic impairment), or pirfenidone titrated over 2 weeks to 801 mg three times daily with food; monitor liver tests monthly for 3 months then every 3 months; manage diarrhoea (loperamide 4 mg then 2 mg after each loose stool, maximum 16 mg daily), nausea and photosensitivity (sun protection).
• Corticosteroids and immunosuppression are not helpful and add infection risk; avoid unless an inflammatory secondary cause exists.
• Pneumothorax: chest drain, early surgical or chemical pleurodesis in recurrent disease, awareness that lungs are stiff and may not re-expand (an air leak may persist).
• Infection: prompt treatment of chest infections with amoxicillin-clavulanate 625 mg three times daily for 7 days; screening for non-tuberculous mycobacteria and Aspergillus; annual influenza and pneumococcal conjugate vaccine.
• Oxygen: long-term oxygen for at least 15 hours daily when PaO2 is 7.3 kPa or less; ambulatory oxygen for exertional desaturation to less than 88%.
• Nutrition: dietitian review, oral supplements and high-protein diet; many patients have a low body mass index.
• Symptom care: pulmonary rehabilitation, morphine 2.5 mg orally every 4 hours as needed (with laxative) for refractory breathlessness, codeine linctus or morphine for cough.
• Lung transplantation: refer early (forced vital capacity of less than 50% predicted or fall of 10%, hypoxia), though the thoracic shape, low weight and recurrent pneumothorax make surgery more difficult; recurrence after transplant has been described.
• Special groups: children (very rare; assess for genetic, post-transplant and infectious causes); pregnancy (high maternal risk with restrictive disease; avoid nintedanib and pirfenidone); elderly (palliative care focus); renal impairment (antifibrotic doses unchanged with mild to moderate impairment, avoid in severe); post-transplant (individualised, immunosuppression by the transplant team).
• Red flags: pneumothorax, rapid decline in forced vital capacity (10% or more in 6 to 12 months), fever and sputum, haemoptysis, weight loss, right heart failure.
• Follow-up: spirometry and diffusing capacity every 3 months, CT at 6 to 12 months, liver tests while on antifibrotics, palliative review; median survival is about 3 to 8 years with wide variation (approximate).