• Borna Mehrad, Marie D Burdick, Nancy J Wandersee, Kaushik S Shahir, Liyun Zhang, Pippa M Simpson, Robert M Strieter, and Joshua J Field.
• Division of Pulmonary & Critical Care Medicine, Department of Medicine, and Beirne B. Carter Center for Immunology, University of Virginia, Charlottesville, VA.
• Blood Adv. 2017 Nov 14; 1 (24): 2217-2224.

AbstractLung injury and fibrosis are common in patients with sickle cell disease (SCD). Fibrocytes, a population of circulating, bone marrow-derived cells, have been linked to development and progression of tissue fibrogenesis and have been implicated in the development of lung fibrosis in preclinical models of SCD. We tested the hypothesis that the levels and activation state of circulating fibrocytes during steady state are associated with abnormal pulmonary function in adults with SCD. In a prospective cohort of steady-state adults with SCD and healthy age- and race-matched control participants, we measured the concentration and activation state of circulating fibrocytes and assessed pulmonary phenotype with pulmonary function tests (PFTs), a respiratory questionnaire, 6-minute walk test, high-resolution chest computed tomography scan, and echocardiogram. Seventy-one adults with SCD and 26 healthy African American control participants were examined. Compared with control participants, patients with SCD demonstrated higher levels of circulating fibrocytes, a significant proportion of which expressed the activation marker α-smooth muscle actin. Within patients with SCD, elevated absolute concentrations of circulating fibrocytes were strongly and independently associated with impaired lung physiology, as measured by PFTs. We conclude that elevated circulating fibrocytes are associated with lung disease in adults with SCD during steady state, consistent with a role for these cells in pathogenesis of lung fibrosis in this disease. Circulating fibrocytes may represent a novel biomarker for progressive pulmonary fibrosis in patients with SCD.

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