How to diagnose and manage acute exacerbation of Idiopathic Pulmonary Fibrosis (IPF)?

Diagnosis and Management of Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Acute exacerbation of IPF should be diagnosed when there is recent worsening of dyspnoea (<30 days) with new ground-glass opacities on imaging, after excluding other causes of respiratory deterioration, and treated with high-dose corticosteroids as the primary pharmacological intervention. 1

Diagnostic Criteria

• Acute exacerbation of IPF is characterized by acute (<30 days) worsening of dyspnoea with no identified cause (infection, pulmonary embolism, left heart failure, or cardiac arrhythmia) in a patient with established IPF 1
• HRCT shows new opacities (particularly ground-glass opacities) in addition to pre-existing fibrotic abnormalities 1
• Worsening hypoxaemia is common (≥10 mmHg decrease in PaO₂) 1
• Diagnostic workup must rule out alternative causes of acute deterioration before confirming acute exacerbation 1

Diagnostic Algorithm

1. Clinical assessment: Evaluate for recent (<30 days) worsening of dyspnoea 1
2. Imaging: Perform HRCT to identify new ground-glass opacities superimposed on UIP pattern 1, 2
3. Rule out alternative causes:
   • Perform CT angiogram to exclude pulmonary embolism 2
   • Obtain cultures and consider bronchoscopy with BAL to exclude infection 2
   • Perform echocardiogram to exclude left heart failure 1, 2
   • Consider other causes like pneumothorax 1

Management Approach

Pharmacological Treatment

• High-dose corticosteroids: Recommended as first-line treatment despite limited evidence from controlled trials 1

  • No specific recommendations exist regarding dose, route, and duration, but intravenous corticosteroids up to 1 gram per day have been reported in case series 1

• Immunosuppressive agents:

  • Intravenous cyclophosphamide may be considered as an adjunctive treatment 1
  • Cyclosporine A has been used but without convincing results 1

• Anticoagulation:

  • Insufficient data regarding the use of low-molecular weight heparin specifically for acute exacerbations 1
  • Long-term oral anticoagulant therapy is not recommended in IPF due to increased mortality 1
  • Anticoagulant therapy may be prescribed if thromboembolic venous disease is suspected 1

• Antibiotics:

  • Wide-spectrum antibiotics may be used when infection has not been definitely ruled out 1

Respiratory Support

• Invasive ventilation:

  • Not recommended in patients with established IPF and acute respiratory failure due to high associated mortality 1
  • May be considered in select cases:
    • As a bridge to lung transplantation 1
    • If exacerbation is the first manifestation of IPF 1
    • In case of acute infection or other reversible cause 1

• Non-invasive ventilation:

  • May be preferred to invasive ventilation in some patients with acute exacerbation 1
  • Limited data suggests it may not increase mortality compared to invasive ventilation 1

Supportive Care

• Oxygen therapy: Provide supplemental oxygen to maintain adequate oxygenation 1
• Pulmonary rehabilitation: Consider in stable patients but may not be feasible during acute exacerbation 1
• Lung transplantation: Consider emergency evaluation in eligible patients (typically <65 years of age) 1

Prognosis and Monitoring

• Acute exacerbations of IPF are associated with high morbidity and mortality 3, 4
• Patients who experience an acute exacerbation show worsened overall prognosis 4
• Risk factors for acute exacerbation include:
  • Poorer baseline lung function 4
  • Presence of comorbidities such as GERD and pulmonary hypertension 4

Prevention Strategies

• Annual influenza vaccination and pneumococcal vaccination 1
• Early consideration of lung transplantation in eligible patients with IPF 1
• Emerging evidence suggests that chronic treatment of IPF with antifibrotic agents may reduce the incidence of acute exacerbations 4

Important Caveats

• Video-assisted surgical lung biopsy is usually considered too hazardous during acute exacerbation and is not recommended 1
• Discussions regarding goals of care, including decisions about mechanical ventilation, should ideally occur during stable clinic visits before an acute exacerbation 1
• The decision to use mechanical ventilation should be made after careful discussion with patients and caregivers regarding goals of care 1
• Despite common use of corticosteroids, evidence supporting their efficacy is limited to anecdotal reports 1, 3