Monocyte counts could predict IPF outcome
medwireNews: Elevated monocyte counts are associated with poor outcomes among patients with idiopathic pulmonary fibrosis (IPF), suggest study findings published in The Lancet Respiratory Medicine.
Using transcriptome data from peripheral blood mononuclear cell (PBMC) samples taken from 120 patients with IPF in their discovery analysis, the researchers found that individuals with an estimated proportion of CD14+ monocytes above the mean had significantly shorter transplant-free survival times then those with CD14+ monocyte percentages below this threshold (hazard ratio [HR] for transplantation or death=1.82).
For instance, 2 years after IPF diagnosis, patients with monocyte percentages above the mean had a transplant-free survival rate of around 50%, compared with approximately 75% for those with percentages below the mean. T-cell and B-cell percentages were not significantly associated with estimated transplant-free survival, however.
Purvesh Khatri, from Stanford University in California, USA, and colleagues then validated these findings using PBMC samples from two independent cohorts of IPF patients. In the first, comprising 45 participants from the COMET trial, patients with progressive disease had significantly higher absolute CD14+ monocyte counts than those with non-progressive disease, at approximately 150,000 versus 350,000 cells.
In the second validation cohort (Yale), CD14+ monocytes accounted for a significantly higher proportion of PBMCs in 15 patients with IPF versus five healthy controls, and the percentage of CD14+ cells rose as mortality risk increased.
Moreover, in an analysis of the medical records of 7459 patients with IPF from three further cohorts (Stanford, Vanderbilt and Optum), the study authors found that individuals with monocyte counts of 0.95 K/μL or above had a higher risk of mortality than those with lower counts after adjustment for age and sex.
Finally, the team showed that monocyte counts of 0.95 K/μL or higher were significantly associated with increased mortality risk after adjustment for known measures of IPF severity, namely forced vital capacity (HR=2.47) and the gender, age, physiology index (HR=2.07). Absolute monocyte count was not significantly associated with mortality risk in matched individuals without IPF, whereas neutrophil counts predicted mortality risk in individuals both with and without IPF.
“Collectively, these results suggest that high absolute monocyte count is an idiopathic pulmonary fibrosis-specific marker of mortality and poor outcomes, whereas high neutrophil count is a general marker of mortality”, write the researchers.
They add that their study “addresses a clinical need for a prognostic biomarker for idiopathic pulmonary fibrosis, which would enable more conscientious allocation of scarce resources”, noting that absolute monocyte count is measured as part of the complete blood count, a “widespread and globally available routine clinical test, making this biomarker inexpensive and easy to implement.”
Michael Kreuter (University of Heidelberg, Germany) and Toby Maher (Royal Brompton Hospital, London, UK) write in an accompanying comment that the study results “could help to pave the way towards personalised medicine for this disease in the future.”
They recommend: “Besides further validation in existing and future cohorts, monocyte counts should be assessed as therapeutic biomarkers in upcoming clinical trials; especially where compounds (such as PBI-4050 and TD139) might be acting, at least partly, on macrophages.”
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