High Monocyte Levels Linked to Poorer Outcomes in IPF, Other Fibrotic Diseases, Study Finds

Blood levels of immune cells called monocytes may help predict disease severity and determine the risk of poor outcomes in patients with idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases, a retrospective study suggests.

The study, “Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study,” was published in the journal The Lancet Respiratory Medicine.

IPF disease severity is often determined by calculating the combined gender, age, and physiology (GAP) index of patients, in addition to lung function measurements. However, since lung function changes are generally better predictors of mortality than initial values, proper assessments with this evaluation approach can take up to six months. Lung function results also can be misleading and confused with coexisting emphysemas, a lung condition caused by damage to the air sacs in the lungs.

Since immune cells such as B-cells, T-cells, neutrophils, and monocytes are known to play important roles in IPF, blood analyses represent possible alternatives for predicting disease outcomes. Immune cell count is a noninvasive and more straightforward approach than the 52-gene signature used to study genomic risk profiles.

In this study, researchers in the U.S. evaluated possible associations between disease outcomes and specific immune cell types from IPF patients’ peripheral blood.

They first gathered publicly available genetic data from 120 IPF patients, which they used to estimate the percentages of 13 types of immune cells in each patient to establish initial (baseline) information for further validation.

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After they concluded this first set of analyses, the team continued assessing immune cell markers in samples from six separate cohort studies including patients with IPF or other fibrotic diseases. The analyses included detailed blood cell data from the COMET trial (NCT01071707) and Yale databases, or from electronic health records with blood cell count data from the Stanford, Northwestern, Vanderbilt, and Optum databases.

While detailed data of the immune cells showed no association between T-cell or B-cell percentages and patient survival, high percentages of monocytes were found to be associated with shorter lung transplant-free survival.

In addition, the data revealed that 29 patients with progressive disease (defined as records of death, lung transplantation, or worsened lung function) had higher monocyte counts than 16 participants with non-progressive disease. Similarly, results from a separate study showed higher percentages of monocytes in 15 IPF patients than in five healthy controls.

Researchers next analyzed electronic health records from 7,459 IPF patients. They found that patients who had higher monocyte count values of 950 monocytes per microliter of blood were at a 1.52 to 2.3 times increased risk of all-cause mortality.

Although neutrophil count was also found to be associated with patient survival, this marker was not specific for IPF. Instead, neutrophil count was a predictor of mortality in non-fibrotic participants.

In contrast, monocyte levels above the cut-off value were only associated with an increased risk of mortality in IPF patients, making these numbers an IPF-specific marker of poor outcomes and death.

Unlike commonly used IPF-related evaluations that test lung function, in which changes from baseline may predict disease severity, the researchers found no link between changes in monocyte levels over time and survival. Results instead showed that monocyte counts were stable, suggesting that IPF patients kept the same risk profile over time.

Data from Stanford, Vanderbilt, and Optum databases showed that a high monocyte count was associated with shortened survival among patients with fibrosis-related diseases, including systemic sclerosis, hypertrophic cardiomyopathy, and myelofibrosis. These results suggested that high monocyte levels may serve as a prognostic marker in IPF and other fibrotic diseases.

“Monocyte count might identify a patient with a fibrotic disease who is at high risk of mortality earlier than fibrotic disease-severity indices [can],” the researchers wrote.

Although monocyte depletion may increase the risk of infection, the study results showed improved survival in IPF patients with normal monocyte levels. Based on this, the team suggested that “reducing monocyte counts of patients to normal range could increase survival without increasing the risk of infection. Hence, selective depletion of monocytes might represent a new avenue of therapy in patients with IPF.”