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Circulating fibrocytes can identify people with a poor prognosis in pulmonary fibrosis

Rationale: Circulating fibrocytes are elevated in idiopathic pulmonary fibrosis, but the relationship between fibrocyte level with lung function decline and clinical outcomes remains controversial. Objective: To provide evidence for the utility of circulating fibrocyte levels as a prognostic biomarker in pulmonary fibrosis. Methods: We tested associations between circulating fibrocyte levels, mortality, disease progression and longitudinal lung function in a well-defined prospective observational study of pulmonary fibrosis (PROFILE; NCT01134822). A subset of recruited participants had blood samples processed for fibrocyte measurement, with flow cytometry based on CD45 and collagen-I gating. Associations were tested using univariate and multivariate generalised linear models. Mortality data were combined with an independent study in a weighted-pooled analysis. Measurements and Main Results: In 119 participants with idiopathic pulmonary fibrosis and non-specific interstitial pneumonia, circulating fibrocytes were elevated but not significantly above healthy controls. In multivariate analyses, each increment in circulating fibrocyte was associated with a 4% increased risk of overall mortality (Hazard Ratio 1.04 95% CI 1.00-1.09). A weighted-pooled analysis of idiopathic pulmonary fibrosis alone supported these observations in a larger sample of 162 participants, a 5% rise in fibrocytes was associated with a 24% increase in adjusted mortality risk (Hazard Ratio 1.24 95% CI 1.06-1.46). We found no association of fibrocytes with lung function or disease progression. Conclusions: In a large prospective clinical cohort of pulmonary fibrosis, circulating fibrocytes can be isolated and increased levels are associated with increased mortality but do not associate with disease related decline in lung function.