Idiopathic pulmonary fibrosis - usual interstitial pneumonia - Restrictive lung disorders

Idiopathic pulmonary fibrosis – usual interstitial pneumonia

Definition

This condition was previously known as cryptogenic fibrosing alveolitis (CFA) characterised by interstitial infiltrates mainly in the lung bases causing progressive dyspnoea. It has been reclassified as usual interstitial pneumonia, a form of idiopathic interstitial pneumonia.

Prevalence

Uncommon.

Age

Usually late middle age.

Sex

Slightly M > F

Aetiology

Unknown, but an indistinguishable disease is seen in association with a number of other diseases such as asbestosis, rheumatoid arthritis and systemic sclerosis. Antinuclear factor is positive in one third of patients and rheumatoid factor is positive in 50%. Up to 75% of patients are current or former smokers, and smoking appears to be an independent risk factor.

Pathophysiology

There appear to be areas of fibroblast activation, which lay down matrix, and healing of these leads to fibrosis. It is not clear what causes the acute lung injury or the abnormal healing process, but increased levels of cytokines and immune cells are found.

Clinical features

Patients present with dry cough and gradually increasing breathlessness. They may present with secondary bacterial infection. Classical signs are clubbing, cyanosis and fine end-inspiratory crackles in the mid to lower lungs.

Microscopy

Characteristically chronic fibrotic, scarred zones with collapsed alveoli and honeycombing alternate with areas of relatively unaffected lung. Where there is acute injury, there are foci of activated fibroblasts with little inflammation.

Complications

The disease is progressive and usually unresponsive to treatment, and patients develop respiratory failure, pulmonary hypertension and cor pulmonale. An acute form exists (Hamman–Rich syndrome or acute interstitial pneumonia) with a very high mortality rate.

Investigations

·        Chest X-ray shows fine reticular shadows, mainly in the bases and peripheral honeycombing.

·        CT scan of the chest show a ground glass appearance in areas of alveolitis with extensive reticular patterns due to fibrosis.

·        Respiratory function tests shows a restrictive pattern with reduced lung volumes, FEV1 and FVC are low but the ratio of the two is normal/high, and gas transfer is reduced. In smokers there may be a superimposed obstructive pattern.

·        Blood gases show hypoxaemia with normal or low carbon dioxide levels.

·        High erythrocyte sedimentation rate (ESR) in up to one third of patients.

·        Broncho-alveolar lavage shows increased cells particularly neutrophils.

·        Lung biopsy is indicated if possible, usually transbronchial via bronchoscopy. Because of the patchy nature of the disease, however, surgical lung biopsy of several sites may be needed.

Management

There are no proven effective treatments. A trial of prednisolone 30 mg is indicated if the diagnosis is not well established in case there is a responsive interstitial pneumonitis. Azathioprine and ciclosporin have also been tried. Supportive treatment includes oxygen, long-term oxygen therapy improves the prognosis by delaying the development of cor pulmonale. Single-lung transplant has been shown to be viable, but most patients have concomitant disease which precludes this.

Prognosis

Median survival of 5 years. Forty per cent die of progressive respiratory failure, most of the others from acute infection or concomitant ischaemic heart disease. Newer anti-fibrotic and immunological therapies are being investigated.