Idiopathic pulmonary fibrosis

The synonymous terms idiopathic pulmonary fibrosis (IPF) and cryptogenic fibrosing alveolitis (CFA) refer to a relentlessly progressive fibrotic lung disorder that is the underlying diagnosis in over one-half of patients presenting with typical clinical features of the ‘CFA clinical syndrome’ (see Chapter 18.11.1). Incidence is about 10 to 15 per 100 000, men are more often affected than women, and it most commonly presents in the seventh and eighth decades. Aetiology remains uncertain.

Clinical features—typical presentation is with progressive exertional dyspnoea, without wheeze, and a nonproductive cough. Digital clubbing is present in over 50% of patients. Very fine end-inspiratory crackles are usually heard bilaterally at the lung bases and become widespread in advanced disease. Central cyanosis and clinical evidence of pulmonary hypertension are late features.

Diagnosis—this requires a surgical biopsy revealing a usual interstitial pneumonia (UIP) histological pattern in association with (1) the absence of other known causes of interstitial lung disease, (2) a restrictive lung function profile, and (3) compatible features on chest radiography or high-resolution CT scans. Diagnosis in the absence of a surgical biopsy requires (1) the absence of other known causes of interstitial lung disease, (2) a restrictive lung function profile, (3) high-resolution CT appearances of predominantly basal reticular abnormalities with honeycombing and little or no ground-glass attenuation, and (4) no features of an alternative diagnosis in transbronchial lung biopsy or bronchoalveolar lavage; together with at least three of the following: (a) age over 50 years, (b) insidious unexplained exertional dyspnoea, (c) duration of illness exceeds 3 months, and (d) predominantly basal or widespread crackles on auscultation of the chest.

Differential diagnosis—the distinction between IPF and fibrotic nonspecific interstitial pneumonia (NSIP) (discussed in Chapter 18.11.1) poses particular difficulty and is crucial because of their very different prognoses: the 5-year survival is 10 to 15% in IPF compared to over 60% in fibrotic NSIP.

Management—in definite IPF there is little evidence that traditional treatment regimens have a major impact on outcome. The use of antioxidant (N-acetylcysteine) and low-dose steroid therapy (prednisolone 10 mg/day), with or without an immunosuppressive agent (azathioprine), appears reasonable and is the therapeutic approach preferred by the authors, and the routine use of such a regimen can be justified when a diagnosis of fibrotic NSIP is possible. In 10 to 15% of patients with IPF there is an accelerated deterioration over several weeks that often leads rapidly to a fatal outcome: intravenous high-dose corticosteroids together with intravenous cyclophosphamide are often used in this circumstance.