User login
, including hypertrophic cardiomyopathy, systemic sclerosis, and myelofibrosis, according to research published in The Lancet Respiratory Medicine.
The data indicate that “a single threshold value of absolute monocyte counts of 0.95 K/mcL could be used to identify high-risk patients with a fibrotic disease,” said Madeleine K. D. Scott, a researcher at Stanford (Calif.) University, and coauthors. The results “suggest that monocyte count should be incorporated into the clinical assessment” and may “enable more conscientious allocation of scarce resources, including lung transplantations,” they said.
While other published biomarkers – including gene panels and multicytokine signatures – may be expensive and not readily available, “absolute monocyte count is routinely measured as part of a complete blood count, an inexpensive test used in clinical practice worldwide,” the authors said.
Further study of monocytes’ mechanistic role in fibrosis ultimately could point to new treatment approaches.
A retrospective multicenter cohort study
To assess whether immune cells may identify patients with idiopathic pulmonary fibrosis at greater risk of poor outcomes, Ms. Scott and her collaborators conducted a retrospective multicenter cohort study.
They first analyzed transcriptome data from 120 peripheral blood mononuclear cell samples of patients with idiopathic pulmonary fibrosis, which they obtained from the Gene Expression Omnibus at the National Center for Biotechnology Information. They used statistical deconvolution to estimate percentages of 13 immune cell types and examined their associations with transplant-free survival. Their discovery analysis found that estimated CD14+ classical monocyte percentages above the mean correlated with shorter transplant-free survival times (hazard ratio, 1.82), but percentages of T cells and B cells did not.
The researchers then validated these results using samples from patients with idiopathic pulmonary fibrosis in two independent cohorts. In the COMET validation cohort, which included 45 patients with idiopathic pulmonary fibrosis whose monocyte counts were measured using flow cytometry, higher monocyte counts were significantly associated with greater risk of disease progression. In the Yale cohort, which included 15 patients with idiopathic pulmonary fibrosis, the 6 patients who were classified as high risk on the basis of a 52-gene signature had more CD14+ monocytes than the 9 low-risk patients did.
In addition, Ms. Scott and her collaborators looked at complete blood count values in the electronic health records of 45,068 patients with idiopathic pulmonary fibrosis, systemic sclerosis, hypertrophic cardiomyopathy, or myelofibrosis in Stanford, Northwestern, Vanderbilt, and Optum Clinformatics Data Mart cohorts.
Among patients in the COMET, Stanford, and Northwestern datasets, monocyte counts of 0.95 K/mcL or greater were associated with mortality after adjustment for forced vital capacity (HR, 2.47) and the gender, age, and physiology index (HR, 2.06). Data from 7,459 patients with idiopathic pulmonary fibrosis “showed that patients with monocyte counts of 0.95 K/mcL or greater were at increased risk of mortality with lung transplantation as a censoring event, after adjusting for age at diagnosis and sex” in the Stanford (HR, 2.30), Vanderbilt (HR, 1.52), and Optum (HR, 1.74) cohorts. “Likewise, higher absolute monocyte count was associated with shortened survival in patients with hypertrophic cardiomyopathy across all three cohorts, and in patients with systemic sclerosis or myelofibrosis in two of the three cohorts,” the researchers said.
The study was funded by grants from the Bill & Melinda Gates Foundation, U.S. National Institute of Allergy and Infectious Diseases, and U.S. National Library of Medicine. Ms. Scott had no competing interests. Coauthors disclosed grants, compensation, and support from foundations, agencies, and companies.
SOURCE: Scott MKD et al. Lancet Respir Med. 2019 Jun. doi: 10.1016/S2213-2600(18)30508-3.
The study by Scott et al. provides evidence that monocyte count may be a “novel, simple, and inexpensive prognostic biomarker in idiopathic pulmonary fibrosis,” according to an accompanying editorial.
Progress has been made in the treatment of idiopathic pulmonary fibrosis, but patient prognosis remains “challenging to predict,” wrote Michael Kreuter, MD, of University of Heidelberg, Germany, and Toby M. Maher, MB, MSc, PhD, of Royal Brompton Hospital in London and Imperial College London. “One lesson that can be learned from other respiratory disorders is that routinely measured cellular biomarkers, such as blood eosinophil counts in chronic obstructive pulmonary disease (COPD), can predict treatment responses” (Lancet Respir Med. 2019 Jun. doi: 10.1016/S2213-2600[19]30050-5).
Increased blood monocyte counts in idiopathic pulmonary fibrosis may reflect disease activity, which “could explain the outcome differences,” said Dr. Kreuter and Dr. Maher. “As highlighted by the investigators themselves, before introducing assessment of monocyte counts as part of routine clinical care for individuals with idiopathic pulmonary fibrosis, the limitations of this research should be taken into account. These include uncertainty around diagnosis and disease severity in a substantial subset of the patients, and the unknown effect of medical therapies (including corticosteroids and immunosuppressant and antifibrotic drugs) on monocyte counts and prognosis.” Researchers should validate the clinical value of blood monocyte counts in existing and future cohorts and evaluate the biomarker in clinical trials.
The editorialists have received compensation and funding from various pharmaceutical companies.
The study by Scott et al. provides evidence that monocyte count may be a “novel, simple, and inexpensive prognostic biomarker in idiopathic pulmonary fibrosis,” according to an accompanying editorial.
Progress has been made in the treatment of idiopathic pulmonary fibrosis, but patient prognosis remains “challenging to predict,” wrote Michael Kreuter, MD, of University of Heidelberg, Germany, and Toby M. Maher, MB, MSc, PhD, of Royal Brompton Hospital in London and Imperial College London. “One lesson that can be learned from other respiratory disorders is that routinely measured cellular biomarkers, such as blood eosinophil counts in chronic obstructive pulmonary disease (COPD), can predict treatment responses” (Lancet Respir Med. 2019 Jun. doi: 10.1016/S2213-2600[19]30050-5).
Increased blood monocyte counts in idiopathic pulmonary fibrosis may reflect disease activity, which “could explain the outcome differences,” said Dr. Kreuter and Dr. Maher. “As highlighted by the investigators themselves, before introducing assessment of monocyte counts as part of routine clinical care for individuals with idiopathic pulmonary fibrosis, the limitations of this research should be taken into account. These include uncertainty around diagnosis and disease severity in a substantial subset of the patients, and the unknown effect of medical therapies (including corticosteroids and immunosuppressant and antifibrotic drugs) on monocyte counts and prognosis.” Researchers should validate the clinical value of blood monocyte counts in existing and future cohorts and evaluate the biomarker in clinical trials.
The editorialists have received compensation and funding from various pharmaceutical companies.
The study by Scott et al. provides evidence that monocyte count may be a “novel, simple, and inexpensive prognostic biomarker in idiopathic pulmonary fibrosis,” according to an accompanying editorial.
Progress has been made in the treatment of idiopathic pulmonary fibrosis, but patient prognosis remains “challenging to predict,” wrote Michael Kreuter, MD, of University of Heidelberg, Germany, and Toby M. Maher, MB, MSc, PhD, of Royal Brompton Hospital in London and Imperial College London. “One lesson that can be learned from other respiratory disorders is that routinely measured cellular biomarkers, such as blood eosinophil counts in chronic obstructive pulmonary disease (COPD), can predict treatment responses” (Lancet Respir Med. 2019 Jun. doi: 10.1016/S2213-2600[19]30050-5).
Increased blood monocyte counts in idiopathic pulmonary fibrosis may reflect disease activity, which “could explain the outcome differences,” said Dr. Kreuter and Dr. Maher. “As highlighted by the investigators themselves, before introducing assessment of monocyte counts as part of routine clinical care for individuals with idiopathic pulmonary fibrosis, the limitations of this research should be taken into account. These include uncertainty around diagnosis and disease severity in a substantial subset of the patients, and the unknown effect of medical therapies (including corticosteroids and immunosuppressant and antifibrotic drugs) on monocyte counts and prognosis.” Researchers should validate the clinical value of blood monocyte counts in existing and future cohorts and evaluate the biomarker in clinical trials.
The editorialists have received compensation and funding from various pharmaceutical companies.
, including hypertrophic cardiomyopathy, systemic sclerosis, and myelofibrosis, according to research published in The Lancet Respiratory Medicine.
The data indicate that “a single threshold value of absolute monocyte counts of 0.95 K/mcL could be used to identify high-risk patients with a fibrotic disease,” said Madeleine K. D. Scott, a researcher at Stanford (Calif.) University, and coauthors. The results “suggest that monocyte count should be incorporated into the clinical assessment” and may “enable more conscientious allocation of scarce resources, including lung transplantations,” they said.
While other published biomarkers – including gene panels and multicytokine signatures – may be expensive and not readily available, “absolute monocyte count is routinely measured as part of a complete blood count, an inexpensive test used in clinical practice worldwide,” the authors said.
Further study of monocytes’ mechanistic role in fibrosis ultimately could point to new treatment approaches.
A retrospective multicenter cohort study
To assess whether immune cells may identify patients with idiopathic pulmonary fibrosis at greater risk of poor outcomes, Ms. Scott and her collaborators conducted a retrospective multicenter cohort study.
They first analyzed transcriptome data from 120 peripheral blood mononuclear cell samples of patients with idiopathic pulmonary fibrosis, which they obtained from the Gene Expression Omnibus at the National Center for Biotechnology Information. They used statistical deconvolution to estimate percentages of 13 immune cell types and examined their associations with transplant-free survival. Their discovery analysis found that estimated CD14+ classical monocyte percentages above the mean correlated with shorter transplant-free survival times (hazard ratio, 1.82), but percentages of T cells and B cells did not.
The researchers then validated these results using samples from patients with idiopathic pulmonary fibrosis in two independent cohorts. In the COMET validation cohort, which included 45 patients with idiopathic pulmonary fibrosis whose monocyte counts were measured using flow cytometry, higher monocyte counts were significantly associated with greater risk of disease progression. In the Yale cohort, which included 15 patients with idiopathic pulmonary fibrosis, the 6 patients who were classified as high risk on the basis of a 52-gene signature had more CD14+ monocytes than the 9 low-risk patients did.
In addition, Ms. Scott and her collaborators looked at complete blood count values in the electronic health records of 45,068 patients with idiopathic pulmonary fibrosis, systemic sclerosis, hypertrophic cardiomyopathy, or myelofibrosis in Stanford, Northwestern, Vanderbilt, and Optum Clinformatics Data Mart cohorts.
Among patients in the COMET, Stanford, and Northwestern datasets, monocyte counts of 0.95 K/mcL or greater were associated with mortality after adjustment for forced vital capacity (HR, 2.47) and the gender, age, and physiology index (HR, 2.06). Data from 7,459 patients with idiopathic pulmonary fibrosis “showed that patients with monocyte counts of 0.95 K/mcL or greater were at increased risk of mortality with lung transplantation as a censoring event, after adjusting for age at diagnosis and sex” in the Stanford (HR, 2.30), Vanderbilt (HR, 1.52), and Optum (HR, 1.74) cohorts. “Likewise, higher absolute monocyte count was associated with shortened survival in patients with hypertrophic cardiomyopathy across all three cohorts, and in patients with systemic sclerosis or myelofibrosis in two of the three cohorts,” the researchers said.
The study was funded by grants from the Bill & Melinda Gates Foundation, U.S. National Institute of Allergy and Infectious Diseases, and U.S. National Library of Medicine. Ms. Scott had no competing interests. Coauthors disclosed grants, compensation, and support from foundations, agencies, and companies.
SOURCE: Scott MKD et al. Lancet Respir Med. 2019 Jun. doi: 10.1016/S2213-2600(18)30508-3.
, including hypertrophic cardiomyopathy, systemic sclerosis, and myelofibrosis, according to research published in The Lancet Respiratory Medicine.
The data indicate that “a single threshold value of absolute monocyte counts of 0.95 K/mcL could be used to identify high-risk patients with a fibrotic disease,” said Madeleine K. D. Scott, a researcher at Stanford (Calif.) University, and coauthors. The results “suggest that monocyte count should be incorporated into the clinical assessment” and may “enable more conscientious allocation of scarce resources, including lung transplantations,” they said.
While other published biomarkers – including gene panels and multicytokine signatures – may be expensive and not readily available, “absolute monocyte count is routinely measured as part of a complete blood count, an inexpensive test used in clinical practice worldwide,” the authors said.
Further study of monocytes’ mechanistic role in fibrosis ultimately could point to new treatment approaches.
A retrospective multicenter cohort study
To assess whether immune cells may identify patients with idiopathic pulmonary fibrosis at greater risk of poor outcomes, Ms. Scott and her collaborators conducted a retrospective multicenter cohort study.
They first analyzed transcriptome data from 120 peripheral blood mononuclear cell samples of patients with idiopathic pulmonary fibrosis, which they obtained from the Gene Expression Omnibus at the National Center for Biotechnology Information. They used statistical deconvolution to estimate percentages of 13 immune cell types and examined their associations with transplant-free survival. Their discovery analysis found that estimated CD14+ classical monocyte percentages above the mean correlated with shorter transplant-free survival times (hazard ratio, 1.82), but percentages of T cells and B cells did not.
The researchers then validated these results using samples from patients with idiopathic pulmonary fibrosis in two independent cohorts. In the COMET validation cohort, which included 45 patients with idiopathic pulmonary fibrosis whose monocyte counts were measured using flow cytometry, higher monocyte counts were significantly associated with greater risk of disease progression. In the Yale cohort, which included 15 patients with idiopathic pulmonary fibrosis, the 6 patients who were classified as high risk on the basis of a 52-gene signature had more CD14+ monocytes than the 9 low-risk patients did.
In addition, Ms. Scott and her collaborators looked at complete blood count values in the electronic health records of 45,068 patients with idiopathic pulmonary fibrosis, systemic sclerosis, hypertrophic cardiomyopathy, or myelofibrosis in Stanford, Northwestern, Vanderbilt, and Optum Clinformatics Data Mart cohorts.
Among patients in the COMET, Stanford, and Northwestern datasets, monocyte counts of 0.95 K/mcL or greater were associated with mortality after adjustment for forced vital capacity (HR, 2.47) and the gender, age, and physiology index (HR, 2.06). Data from 7,459 patients with idiopathic pulmonary fibrosis “showed that patients with monocyte counts of 0.95 K/mcL or greater were at increased risk of mortality with lung transplantation as a censoring event, after adjusting for age at diagnosis and sex” in the Stanford (HR, 2.30), Vanderbilt (HR, 1.52), and Optum (HR, 1.74) cohorts. “Likewise, higher absolute monocyte count was associated with shortened survival in patients with hypertrophic cardiomyopathy across all three cohorts, and in patients with systemic sclerosis or myelofibrosis in two of the three cohorts,” the researchers said.
The study was funded by grants from the Bill & Melinda Gates Foundation, U.S. National Institute of Allergy and Infectious Diseases, and U.S. National Library of Medicine. Ms. Scott had no competing interests. Coauthors disclosed grants, compensation, and support from foundations, agencies, and companies.
SOURCE: Scott MKD et al. Lancet Respir Med. 2019 Jun. doi: 10.1016/S2213-2600(18)30508-3.
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: An increased monocyte count predicts poor outcomes among patients with idiopathic pulmonary fibrosis and other fibrotic diseases.
Major finding: Among patients in three cohorts, monocyte counts of 0.95 K/mcL or greater were associated with mortality after adjustment for forced vital capacity (hazard ratio, 2.47) and the gender, age, and physiology index (HR, 2.06).
Study details: A retrospective analysis of data from 7,000 patients with idiopathic pulmonary fibrosis from five independent cohorts.
Disclosures: The study was funded by grants from the Bill & Melinda Gates Foundation, U.S. National Institute of Allergy and Infectious Diseases, and U.S. National Library of Medicine. Ms. Scott had no competing interests. Coauthors disclosed grants, compensation, and support from foundations, agencies, and companies.
Source: Scott MKD et al. Lancet Respir Med. 2019 Jun. doi: 10.1016/S2213-2600(18)30508-3.