Acute Interstitial Pneumonia

Acute interstitial pneumonia is a rapidly progressive idiopathic lung injury that presents as acute respiratory distress syndrome, with diffuse alveolar damage on histology and no identifiable cause. It was previously called Hamman-Rich syndrome.

It affects adults of about 50 years, both sexes, often with a flu like prodrome of 1 to 2 weeks. Mortality is high, at about 50 to 70%, and most deaths occur within 3 months. It is a diagnosis of exclusion.

Pathophysiology. Diffuse epithelial and endothelial injury leads to hyaline membranes, alveolar oedema and, later, organising fibroblast proliferation. The initiating cause is unknown. Similar patterns arise from infection, drugs, connective tissue disease, toxins and the acute exacerbation of fibrotic lung disease, which must be excluded.

Fever, cough and rapidly progressive dyspnoea over days to 3 weeks, followed by hypoxaemic respiratory failure that needs mechanical ventilation in most. Examination shows tachypnoea, bilateral crackles and cyanosis.

Hypoxaemia, tachypnoea and exhaustion need immediate critical care, since patients can deteriorate in hours.

• Chest radiograph: bilateral diffuse airspace opacities. High resolution CT: bilateral ground glass and consolidation, with a gravity dependent pattern, and traction bronchiectasis in the organising phase.
• Arterial blood gas: PaO2/FiO2 usually under 40 kPa (300 mmHg), and often under 26.7 kPa (200 mmHg).
• Exclude infection and other causes: blood and sputum cultures, respiratory viral PCR, Pneumocystis testing, bronchoalveolar lavage with microscopy and culture, cardiac evaluation (echocardiography, natriuretic peptide) to exclude heart failure, and urine antigens.
• Serology for connective tissue disease and vasculitis (antinuclear antibody, anti-neutrophil cytoplasmic antibody, myositis antibodies), drug and exposure history, and HIV test.
• Surgical or transbronchial biopsy only when feasible and safe, showing diffuse alveolar damage.

Differential diagnosis.

• Acute respiratory distress syndrome from a known cause (sepsis, pneumonia, aspiration, trauma, pancreatitis)
• Acute exacerbation of idiopathic pulmonary fibrosis or other fibrosing disease
• Acute eosinophilic pneumonia
• Diffuse alveolar haemorrhage
• Cardiogenic pulmonary oedema
• Viral and Pneumocystis pneumonia
• Drug induced lung injury

• Intensive care with lung protective ventilation: tidal volume 6 mL/kg ideal body weight, plateau pressure under 30 cm H2O, adequate PEEP, and prone positioning for at least 12 to 16 hours daily when PaO2/FiO2 is under 20 kPa (150 mmHg). Conservative fluid management, and neuromuscular blockade in severe cases.
• Empirical antimicrobials until infection is excluded: ceftriaxone 2 g intravenously daily with azithromycin 500 mg intravenously daily, with Pneumocystis cover (co-trimoxazole 15 to 20 mg/kg/day of trimethoprim in 3 to 4 divided doses) when immunosuppression or HIV is possible, and oseltamivir 75 mg twice daily during influenza season.
• Corticosteroid is usual practice, though evidence is limited: methylprednisolone 500 to 1000 mg intravenously daily for 3 days, then prednisolone 1 mg/kg daily, tapered over 2 to 3 months, with early review of the response over 3 to 7 days.
• Rescue options in selected patients: cyclophosphamide 500 mg/m2 intravenously, or other immunosuppression, and venovenous extracorporeal membrane oxygenation in young patients with potentially reversible disease.
• Supportive care: stress ulcer prophylaxis, thromboprophylaxis with enoxaparin 40 mg subcutaneously daily (20 mg at eGFR under 30), glycaemic control, nutrition and early mobilisation.
• Survivors: pulmonary rehabilitation and follow up for residual fibrosis.

Complications and prognosis. Mortality is 50 to 70%. Survivors often recover near normal lung function, though recurrence and progression to fibrosis occur in some.

Monitoring. Daily arterial gases, chest imaging and organ support in intensive care, then spirometry and CT at 3 months, 6 months and 12 months after discharge.

Referral and escalation. Refer immediately to intensive care, and to an interstitial lung disease service for follow up.