Are we pro-PRO-C4?

Fibroblastic foci—the cardinal feature of usual interstitial pneumonia (UIP)—are characterised by metaplastic alveolar epithelium overlying tufts of fibroblasts. UIP is further characterised by epithelial cell dropout and a denuded basement membrane.1 Can these histological features be measured as biomarkers of the severity of idiopathic pulmonary fibrosis (IPF)? The classic reference from 25 years ago suggests that the number of fibroblastic foci on histopathology predicts the prognosis in IPF.2 This, of course, requires a biopsy. In this issue of Thorax , Sand and colleagues have essentially reasked this old question.3 Instead of looking at the number of fibroblastic foci, the team has focused on the denuded basement membrane. The basement membrane is composed of collagen IV, which must be synthesised, broken down and resynthesised. Is the turnover of collagen IV in the basement membrane quantifiable? Capitalising on the unique assays available at Nordic Biosciences, the investigators determined if PRO-C4, a serologic marker of type IV collagen turnover, was associated with lung function decline in IPF. PRO-C4 levels were analysed in two prospective, multicentre, longitudinal cohorts of patients with IPF (NCT02755441, NCT01134822, NCT01110694 …