Classically, IPF/UIP is a disease of unknown cause or association characterised by slowly progressive breathlessness and crackles on auscultation of the chest in individuals aged >50 years. The major and minor diagnostic criteria are shown in box 1. The clinical course is variable, but the long‐term survival is poor with only 20–30% survival 5 years after the time of diagnosis.
Box 1 Defining criteria for idiopathic pulmonary fibrosis
- Exclusion of other known causes of interstitial lung disease such as certain drug toxicities, environmental exposures and connective tissue diseases.
- Abnormal pulmonary function studies that include evidence of restriction (reduced vital capacity often with an increased forced expiratory volume in 1 s/forced vital capacity ratio) and impaired gas exchange (increased alveolar–arterial oxygen tension difference with rest or exercise or decreased carbon monoxide transfer factor).
- Bibasilar reticular abnormalities with minimal ground‐glass opacities on high‐resolution CT scans.
- Transbronchial lung biopsy or bronchoalveolar lavage fluid showing no features to support an alternative diagnosis.
- Age >50 years.
- Insidious onset of otherwise unexplained dyspnoea on exertion.
- Duration of illness 3 months.
- Bibasilar inspiratory crackles (dry or “Velcro” type in quality).
Reproduced with permission from American Thoracic Society.28
Key features on high‐resolution CT (HRCT) scanning are a peripheral distribution of disease predominantly at the bases consisting of a reticular pattern with honeycombing. There is little or no ground‐glass opacification, nodules or significant hilar or mediastinal lymphadenopathy (fig 2).
Figure 2Typical CT scan from a patient with idiopathic pulmonary fibrosis. Note the peripheral distribution of disease, the coarse reticular pattern with honeycombing and the absence of much ground‐glass change.
Key histological features of the UIP pattern are patchy geographical distribution and heterogeneity in terms of the stage of pathology in different regions of the biopsy specimen (table 2). There is honeycombing, relatively little cellular inflammation and regions of proliferating myofibroblasts known as fibroblastic foci. Areas of normal lung should be present, in the absence of which the histopathological pattern may be difficult to define. In the past it was commonly stated that the UIP pattern could be found in collagen vascular disease, drug toxicity, asbestosis, chronic hypersensitivity pneumonitis and rare syndromes such as familial IPF and the Hermansky‐Pudlak syndrome. However, using the more strict histopathological criteria, as defined here, has resulted in much less overlap. Commonly, the only features that raise the question of whether or not the UIP pattern is present in many of these situations is the presence of dense end‐stage fibrotic changes without the presence of any other distinguishing features, especially fibroblastic foci. More importantly, these entities often have other features that allow recognition that the pattern is not UIP alone (such as asbestos bodies, ill‐formed granulomas, marked interstitial chronic inflammation, prominent lymphoid follicles or organising pneumonia).
Table 2Distinguishing clinical features of idiopathic pulmonary fibrosis (IPF) and non‐specific interstitial pneumonia (NSIP)