Background
A biomarker that predicts poor asthma control would be clinically useful. Fibrocytes are bone marrow–derived circulating progenitor cells that have been implicated in tissue fibrosis and TH2 responses in asthmatic patients.
Objective
We sought to test the hypothesis that the concentration and activation state of peripheral blood fibrocytes correlates with asthma severity.
Methods
By using fluorescence-activated cell sorting analysis, fibrocytes (CD45+ and collagen 1 [Col1]+) were enumerated and characterized in the buffy coats of fresh peripheral blood samples from 15 control subjects and 40 asthmatic patients.
Results
Concentrations of peripheral blood total (CD45+Col1+), activated (the TGF-β transducing protein phosphorylated SMAD2/3 [p-SMAD2/3]+ or phosphorylated AKT [p-AKT]+), and differentiated (α-smooth muscle actin [α-SMA]+) fibrocytes were increased in asthmatic patients compared with control subjects. The increase in total and CD45+Col1+CXCR4+ fibrocytes was primarily seen in patients with severe asthma (Global Initiative for Asthma steps 4–5) as opposed to those with milder asthma (Global Initiative for Asthma steps 1–3). In addition, numbers of circulating α-SMA+ and α-SMA+CXCR4+ fibrocytes were increased in asthmatic patients experiencing an asthma exacerbation in the preceding 12 months. A significant correlation (P <.05) was observed between CD45+Col1+CXCR4+ fibrocytes and the activation phenotypes CD45+Col1+p-SMAD2/3+ and CD45+Col1+p-AKT+.
Conclusion
There was correlation between circulating fibrocyte subsets and asthma severity, and there was an increased number of activated/differentiated fibrocytes in circulating blood of asthmatic patients experiencing an exacerbation in the preceding 12 months.
A 38-year-old African American, HIV-positive man (CD4 count, 347 cells/ml; viral load, 633,000 copies/ml), having never received highly active antiretroviral therapy, presented with several months of nonproductive cough. He had no other past medical history. Computed tomography of the chest ( Figure 1) demonstrated innumerable miliary nodules. Bronchoalveolar lavage (BAL) was performed and contained 71% neutrophils, 13% lymphocytes, and 12% alveolar macrophages. Flow cytometry was not performed. Bacterial, acid-fast bacilli, and fungal smears were negative, and no organisms grew on culture. Pneumocystis carinii pneumonia direct fluorescence antibody and respiratory virus polymerase chain reaction were also negative. An open-lung biopsy specimen stained with hematoxylin and eosin (Figure 2; Figure E1 in the online supplement) showed hyperplastic peribronchovascular lymphoid follicles, follicular bronchiolitis. Bacterial, acid-fast bacilli, and fungal cultures of the biopsy specimen were without growth.
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