Inflammatory leukocyte phenotypes correlate with disease progression in idiopathic pulmonary fibrosis
© 2014 Moore, Fry, Zhou, Murray, Han, Martinez, Flaherty and The COMET Investigators. Idiopathic pulmonary fibrosis (IPF) is characterized by progressive deposition of extracellular matrix, worsening dyspnea, and eventual mortality. Pathogenesis of IPF is poorly understood and the role inflammation and activated leukocytes play in the disease process is controversial. Previous studies demonstrated that activated leukocyte subsets characterize IPF patients. We sought to validate this observation in a well-defined cohort of 35 IPF patients and to correlate the observed leukocyte phenotypes with robust parameters of disease progression. We demonstrate that in univariate and multivariate analyses, increases in the CD14hi, CD16hi subset of monocytes measured at baseline correlated with disease progression, with a threshold value > 0.5% of the total peripheral blood mononuclear cells being a significant predictor for worse outcome. In addition, several T cell subsets, including CD25 expressing CD4 cells, and CXCR3 expressing CD4 and CD8 subsets correlated with disease progression when found in increased percentages in the peripheral blood of IPF patients when sampled at baseline. Somewhat surprising in comparison to previous literature, the CD4 T cells did not appear to have lost expression of the co-stimulatory molecule, CD28, but the CD8 T cells did. Taken together, these results are consistent with the presence of an inflammatory process in IPF patients who eventually progress. However, when longitudinal measurements of these same markers were examined, there was significant heterogeneity of expression and these biomarkers did not necessarily remain elevated in IPF patients with progressive disease. We interpret this heterogeneity to suggest that IPF patients experience episodic inflammatory events that once triggered, may lead to disease progression. This longitudinal heterogeneity in biomarker analyses may explain why such markers are not consistently measured in all IPF cohorts.
Moore, BB; Fry, C; Zhou, Y; Murray, S; Han, MLK; Martinez, FJ; Flaherty, KR; Dushay, K; Kurtis, J; Chapman, JT; Anstrom, K; Brown, KK; Cosgrove, G; Solomon, J; Swigris, J; Fernandez-Perez, E; Criner, G; Cordova, F; Patel, N; Rogers, T; Belperio, J; King, TE; Collard, HR; Noth, I; Brown, C; Garcia, JGN; Kyle Hogarth, D; Huang, Y; Lussier, Y; Ma, SF; Wade, M; Toews, GB; White, ES; Hogaboam, C; Lama, V; Moore, T; Spino, C; Loyd, JE
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