Unclassified or unclassifiable interstitial lung disease: confusing or helpful disease category?

Since the seminal report by Averill A. Liebow in 1968 [1] of the first classification of idiopathic interstitial pneumonias (IIPs), consisting of five entities including ‘‘usual or classical interstitial pneumonia’’ (UIP), a secure diagnosis has, until recently, required histopathological evaluation. A histologically based classification might appear paradoxical, as a biopsy is performed in only a minority of the cases in most centres. Nevertheless, this approach has provided essential guidance for clinicians with regard to: 1) possible aetiology (e.g. a pattern of nonspecific interstitial pneumonia (NSIP) is not necessarily idiopathic but may be related to connective tissue disease (CTD), exposure to drugs, or antigens); 2) prognostic evaluation, largely based on the distinction between idiopathic pulmonary fibrosis (IPF) and the clinical entities associated with other histological patterns; and 3) management, with a strategic choice between antiinflammatory/immunosuppressive therapy, and, in IPF, an anti-fibrotic approach, with pirfenidone currently the only commercially available agent with an established treatment effect.