Fibrothorax due to Tuberculosis

Dense fibrous thickening of the visceral and parietal pleura after tuberculous pleural effusion or empyema, encasing the lung ("pleural peel"), restricting lung expansion and contracting the hemithorax. Trapped lung is a related state in which the visceral pleural peel prevents re-expansion without the chest wall contracting.

• Tuberculosis is the leading cause of pleural effusion and a major cause of fibrothorax in Africa and Asia. Tuberculous pleurisy occurs in about 3 to 5% of tuberculosis cases and about 10 to 20% of extrapulmonary disease, and is more frequent in HIV. About 10 to 50% of patients are left with residual pleural thickening after treatment (mostly mild), and a minority (about 5 to 10%) develop restrictive impairment.
• Risk factors for fibrothorax: delayed diagnosis and treatment, large or loculated effusion, high pleural fluid LDH and low pH or glucose, tuberculous empyema, incomplete drainage, secondary bacterial infection, and HIV.
• Mechanism: delayed hypersensitivity and fibrin deposition produce organised fibrous tissue and collagen, which matures over weeks to months to a rigid peel, often calcified. Reduced lung volume and impaired chest wall movement give a restrictive defect and ventilation to perfusion mismatch.
• Active tuberculosis may persist inside the peel (chronic empyema), and an infected peel can cause bronchopleural fistula and empyema necessitans.

• Exertional breathlessness, chest tightness or pain, cough, reduced exercise tolerance; some are asymptomatic. Fever and weight loss suggest active infection.
• Signs: flattened or retracted hemithorax with crowded ribs, reduced chest expansion, tracheal and mediastinal shift toward the affected side, stony dullness, reduced breath sounds, scoliosis concave to the diseased side, raised hemidiaphragm; clubbing is rare.
• Differential diagnosis: malignant pleural disease and mesothelioma (nodular, circumferential or mediastinal pleural thickening, more than 1 cm), asbestos related pleural disease, post-empyema thickening of other causes, post-haemothorax fibrothorax, pulmonary fibrosis, lung collapse from bronchial obstruction, chronic empyema, aspergilloma in a residual cavity and radiation fibrosis.
• Complications: restrictive respiratory failure, pulmonary hypertension and cor pulmonale, chronic empyema, bronchopleural fistula, empyema necessitans, recurrent chest infection, aspergilloma, and spinal deformity.

• Chest X-ray: pleural thickening, calcification (in about 20 to 30%), volume loss, crowded ribs, mediastinal shift toward the lesion, raised diaphragm, residual effusion.
• Contrast CT chest: smooth pleural thickening greater than 3 mm, a rind over the visceral surface, calcification, residual loculated fluid, trapped lung, fistula, aspergilloma, chest wall extension. Features suggesting malignancy: nodularity, thickness greater than 1 cm, circumferential involvement and mediastinal pleural involvement; biopsy is needed if present.
• Lung function: restrictive pattern (reduced forced vital capacity and total lung capacity, normal or high FEV1/FVC ratio, reduced diffusing capacity); ventilation and perfusion scan shows reduced function in the affected lung to estimate postoperative benefit; six minute walk test; arterial blood gas.
• Look for active tuberculosis: sputum or pleural fluid Xpert MTB/RIF, smear and culture, pleural fluid adenosine deaminase, HIV test, and CRP. Echocardiography for pulmonary hypertension.
• Pleural manometry and ultrasound can show pleural elastance and trapped lung when a residual effusion is present.

• Treat active tuberculosis and prevent progression:
  • Rifampicin 10 mg/kg (maximum 600 mg), isoniazid 5 mg/kg (maximum 300 mg), pyrazinamide 25 mg/kg (maximum 2 g) and ethambutol 15 mg/kg (maximum 1.2 g) daily for 2 months, then rifampicin and isoniazid daily for 4 months (extend the continuation phase to 7 months, 9 months in total, for empyema), with pyridoxine 25 to 50 mg daily. Fixed dose combination tablets are used by weight band. Monitor liver function at 2 and 4 weeks and monthly thereafter when risk factors exist.
  • In HIV, start antiretroviral therapy within 2 weeks if CD4 count is less than 50 per microlitre, and within 8 weeks otherwise; use dolutegravir 50 mg twice daily during rifampicin therapy.
  • Early and complete drainage of a large or loculated tuberculous effusion (therapeutic thoracentesis, or chest drain) may reduce residual thickening; evidence is mixed. Prednisolone does not reduce residual pleural thickening, so do not give it for that purpose (corticosteroids are used only for tuberculous pericarditis or meningitis, and with caution in HIV).
  • Intrapleural fibrinolytics (urokinase 100,000 units or streptokinase 250,000 units daily for 3 days) have been used for loculated tuberculous effusion; evidence is limited.
• Rehabilitation (all patients):
  • Chest physiotherapy, breathing exercises and incentive spirometry, thoracic expansion exercises, graded exercise training, nutrition (30 to 35 kcal/kg/day and 1.2 to 1.5 g/kg/day of protein), smoking cessation, and long term oxygen when PaO2 is 7.3 kPa or less.
  • Vaccination: yearly influenza, pneumococcal conjugate vaccine.
  • Treat complications: antibiotics for secondary infection (co-amoxiclav 625 mg three times daily for 7 to 14 days), tranexamic acid 1 g every 8 hours for haemoptysis (evidence is limited), and bronchial artery embolisation for significant haemoptysis.
• Surgery for symptomatic restriction with a mature peel and expected lung re-expansion (usually 3 to 6 months after onset, after at least 2 months of effective anti-tuberculosis treatment):
  • Decortication by thoracoscopy or thoracotomy (removal of the visceral peel to free the lung), with removal of parietal thickening when needed. Candidates: forced vital capacity less than 50 to 60% predicted with symptoms, chronic tuberculous empyema, trapped lung with persisting effusion, infection that cannot be controlled, or pain. Benefit is greatest when the underlying lung is healthy (confirmed by perfusion on scan or CT). Forced vital capacity improves by about 20 to 50% in many patients; operative mortality about 2 to 5%; complications include prolonged air leak (about 10 to 20%), bleeding, residual space, empyema and bronchopleural fistula.
  • Chronic empyema with fistula or a rigid space: open window thoracostomy (Eloesser flap), muscle flap or omental flap transposition, and thoracoplasty to collapse the space; pleurectomy and lung resection for destroyed lung (lobectomy or pneumonectomy) with active disease.
  • Contraindications to surgery: poor cardiopulmonary reserve (predicted postoperative FEV1 less than 40%), uncontrolled tuberculosis or sepsis, severe pulmonary hypertension and a lung that cannot expand (destroyed parenchyma).
  • Postoperative care: drain with suction at 10 to 20 cmH2O, epidural or paravertebral analgesia (bupivacaine 0.25% infusion), paracetamol 1 g four times daily, ibuprofen 400 mg three times daily if the kidneys allow, morphine 2.5 to 5 mg, enoxaparin 40 mg SC daily, intensive physiotherapy, and continued anti-tuberculosis therapy.
• Special groups:
  • HIV: higher risk of drug interactions; adjust antiretroviral therapy and monitor for immune reconstitution inflammatory syndrome (fever and worsening pleural disease after starting antiretroviral therapy, managed with prednisolone 40 mg daily for 2 weeks then 20 mg daily for 2 weeks, with specialist advice).
  • Children: early drainage and anti-tuberculosis therapy by weight (rifampicin 15 mg/kg, isoniazid 10 mg/kg, pyrazinamide 35 mg/kg, ethambutol 20 mg/kg daily); surgery is deferred where possible.
  • Pregnancy: isoniazid, rifampicin, pyrazinamide and ethambutol are acceptable (avoid streptomycin) with pyridoxine; defer elective decortication until after delivery.
  • Diabetes: strict glucose control improves healing and reduces relapse.
  • Renal impairment: adjust ethambutol and pyrazinamide (three times weekly dosing when creatinine clearance is less than 30 mL/min).
• Red flags: haemoptysis, fever and purulent drainage, chest wall swelling, worsening dyspnoea, nodular pleural thickening on CT (consider mesothelioma or cancer), new hypoxaemia.
• Follow up: review monthly during treatment with sputum and weight; chest X-ray at 2, 6 and 12 months; spirometry at 6 and 12 months; CT if symptoms change; after surgery review at 2 weeks, 3 and 6 months with lung function; lifelong follow up for recurrence and aspergilloma.