Monocyte Count as a Prognostic Biomarker in Patients with Idiopathic Pulmonary Fibrosis

Abstract

Rationale: There is an urgent need for simple, cost-effective prognostic biomarkers for idiopathic pulmonary fibrosis (IPF); biomarkers that show potential include monocyte count. Objectives: We used pooled data from pirfenidone and IFNγ-1b trials to explore the association between monocyte count and prognosis in patients with IPF. Methods: This retrospective pooled analysis included patients (active and placebo arms) from the following four phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in FVC% predicted, ≥50 m decline in 6-minute-walk distance, or death), all-cause hospitalization, and all-cause mortality over 1 year. The relationship between monocyte count (defined as time-dependent) and outcomes was assessed using bivariate and multivariable models. Measurements and Main Results: This analysis included 2,067 patients stratified by monocyte count (at baseline: <0.60 × 10 9 cells/L [ n = 1,609], 0.60 to <0.95 × 10 9 cells/L [ n = 408], and ≥0.95 × 10 9 cells/L [ n = 50]). In adjusted analyses, a higher proportion of patients with monocyte counts of 0.60 to <0.95 × 10 9 cells/L or ≥0.95 × 10 9 cells/L versus <0.60 × 10 9 cells/L experienced IPF progression ( P = 0.016 and P = 0.002, respectively), all-cause hospitalization ( P = 0.030 and P = 0.003, respectively), and all-cause mortality ( P = 0.005 and P < 0.001, respectively) over 1 year. Change in monocyte count from baseline was not associated with any of the outcomes over 1 year and did not appear to be affected by study treatment. Conclusions: In patients with IPF, elevated monocyte count was associated with increased risks of IPF progression, hospitalization, and mortality. Monocyte count may provide a simple and inexpensive prognostic biomarker in IPF.

Monocyte and macrophage derived myofibroblasts: Is it fate? A review of the current evidence

“…13 These circulating cells are thought to extravasate from the circulation into injured and inflammatory areas where they can differentiate into myofibroblasts and contribute to extracellular matrix (ECM) deposition. 14 These ideas are consistent with recent findings whereby circulating monocytes have been identified to be increased and associated with lower survival in a variety of fibrotic diseases [15][16][17] ; however, the differences between monocytes and fibrocytes have not been clearly delineated.…”

The Aggregate Index of Systemic Inflammation (AISI): A Novel Prognostic Biomarker in Idiopathic Pulmonary Fibrosis

“…Although the pathophysiology of IPF remains to be fully elucidated, several immune cells are likely to be involved, particularly lymphocytes, neutrophils, and monocytes. Alterations in lymphocytes and neutrophils levels have previously been reported in IPF [20,21], as well as the association between increased monocytes values and poor prognosis [37]. Therefore, a predictive tool such as the AISI, that includes lymphocytes, neutrophils, platelets, and monocytes, might be superior to simpler indexes as it better reflects the inflammatory status in the context of specific disease states.…”

Biomarkers in Progressive Fibrosing Interstitial Lung Disease: Optimizing Diagnosis, Prognosis, and Treatment Response

“…Monocyte count, obtained as part of a complete blood count, was recently shown to predict increased mortality across multiple IPF cohorts ( 155 ). Kreuter et al also showed increasing monocyte count to predict near-term hospitalization and IPF progression, as measured by death, decreasing walk distance or ≥10% categorical decline in FVC ( 156 ). Because FVC decline is among the earliest objective indicators of a progressive phenotype and change in FVC among the most commonly utilized primary endpoint in clinical trials, biomarkers predictive of FVC decline are of particular importance for identifying early progression and enriching clinical trial cohorts.…”