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A low lymphocyte-to-monocyte ratio (LMR) is associated with worse survival in newly-diagnosed patients with idiopathic pulmonary fibrosis (IPF), according to a new retrospective, single-center analysis. Patients with both IPF and lung cancer also had a lower LMR than patients with IPF alone.
The study, published online in Respiratory Medicine, was conducted among 77 newly diagnosed patients, 40 end-stage IPF patients, and 17 patients with IPF and lung cancer. All received at least 1 year of antifibrotic therapy (pirfenidone or nintedanib). The researchers collected demographic and clinical data between December 2014 and December 2020.
The disease course of IPF is difficult to predict, with some patients progressing slowly, and others suffer a rapid decline to respiratory failure. Previous studies found that higher levels of monocytes are associated with higher mortality in IPF and other fibrotic lung disease, and both neutrophil-to-lymphocyte ratio (NLR) and LMR have been shown to predict mortality in lung cancer.
A previous study found that IPF patients had a higher NLR and a lower LMR than controls, but that research did not consider the impact of antifibrotic treatment, which may improve outcomes.
There has been accumulating cellular and molecular evidence that leukocyte population abnormalities are associated with IPF outcomes, but that work was more discovery based and relied on tests that aren’t readily available clinically, said Erica L. Herzog, MD, PhD, who was asked to comment on the study. “It’s provided a lot of insight into potential new mechanisms and potential biomarkers, but their clinical utility for patients is limited. So the use of lymphocyte-to-monocyte ratios that can be obtained from a complete blood cell count, which is a test that can be done in any hospital, would really be a game-changer in terms of predictive algorithms for patients with IPF,” said Dr. Herzog, who is a professor of medicine and pathology at Yale University, New Haven, Conn., and director of the Yale ILD Center of Excellence.
In humans, abnormalities in circulating monocytes and lymphocytes have individually been linked worse IPF outcomes. Animal studies have implicated monocyte-derived cells in lung fibrosis, but because animal studies have shown that lymphocyte populations are not required for fibrosis, more work is needed.
“I think what we’re finding is that lymphocytes probably have a regulatory role, and there’s probably a protective population and potentially a pathogenic population. Something about the balance between adaptive immunity, which is reflected by your lymphocytes, and innate immunity, which is reflected by your monocytes. Something about that balance is important for tissue homeostasis, and then when it’s disrupted or perturbed, fibrosis ensues,” said Dr. Herzog.
Study details
The newly diagnosed patients were older (mean age, 70 years) than the end-stage IPF patients (mean age, 60 years) and patients with IPF and lung cancer (mean age, 64 years; P < .0001).
Among newly diagnosed IPF patients, a receiving operating characteristic analysis before antifibrotic treatment determined a cutoff LMR value of less than 4.18, with an area under the curve of 0.67 (P = .025). Values below 4.18 were associated with shorter survival (hazard ratio, 6.88; P = .027).
Patients with LMR less than 4.18 were more likely to be men (89% vs. 67%; P = .036), had a lower percent predicted forced vital capacity (76% vs. 87%; P = .023), and were more likely to die or undergo lung transplant (34% vs. 5%; P = .009).
Mortality results
A Kaplan-Meier curve illustrated a stark difference between patients with LMR of 4.18 or higher, nearly all of whom remained alive out to almost 100 months of follow-up. Around 30% of those with LMR less than 4.18 remained alive while close to 100% of the patients with LMR below this value showed worsened outcomes. “You don’t normally see curves like that,” said Dr. Herzog.
There was no significant difference in blood cell counts and ratios at the time of IPF diagnosis and after 1 year of antifibrotic treatment, which suggests that the risk profile is independent of treatment, according to the study authors.
Among patient subgroups, those with IPF and lung cancer had the lowest mean LMR (2.2), followed by newly diagnosed patients (3.5), and those with end-stage disease (3.6; P < .0001).
The study authors reported financial relationships with various pharmaceutical companies. Dr. Herzog had no relevant financial disclosures.
A low lymphocyte-to-monocyte ratio (LMR) is associated with worse survival in newly-diagnosed patients with idiopathic pulmonary fibrosis (IPF), according to a new retrospective, single-center analysis. Patients with both IPF and lung cancer also had a lower LMR than patients with IPF alone.
The study, published online in Respiratory Medicine, was conducted among 77 newly diagnosed patients, 40 end-stage IPF patients, and 17 patients with IPF and lung cancer. All received at least 1 year of antifibrotic therapy (pirfenidone or nintedanib). The researchers collected demographic and clinical data between December 2014 and December 2020.
The disease course of IPF is difficult to predict, with some patients progressing slowly, and others suffer a rapid decline to respiratory failure. Previous studies found that higher levels of monocytes are associated with higher mortality in IPF and other fibrotic lung disease, and both neutrophil-to-lymphocyte ratio (NLR) and LMR have been shown to predict mortality in lung cancer.
A previous study found that IPF patients had a higher NLR and a lower LMR than controls, but that research did not consider the impact of antifibrotic treatment, which may improve outcomes.
There has been accumulating cellular and molecular evidence that leukocyte population abnormalities are associated with IPF outcomes, but that work was more discovery based and relied on tests that aren’t readily available clinically, said Erica L. Herzog, MD, PhD, who was asked to comment on the study. “It’s provided a lot of insight into potential new mechanisms and potential biomarkers, but their clinical utility for patients is limited. So the use of lymphocyte-to-monocyte ratios that can be obtained from a complete blood cell count, which is a test that can be done in any hospital, would really be a game-changer in terms of predictive algorithms for patients with IPF,” said Dr. Herzog, who is a professor of medicine and pathology at Yale University, New Haven, Conn., and director of the Yale ILD Center of Excellence.
In humans, abnormalities in circulating monocytes and lymphocytes have individually been linked worse IPF outcomes. Animal studies have implicated monocyte-derived cells in lung fibrosis, but because animal studies have shown that lymphocyte populations are not required for fibrosis, more work is needed.
“I think what we’re finding is that lymphocytes probably have a regulatory role, and there’s probably a protective population and potentially a pathogenic population. Something about the balance between adaptive immunity, which is reflected by your lymphocytes, and innate immunity, which is reflected by your monocytes. Something about that balance is important for tissue homeostasis, and then when it’s disrupted or perturbed, fibrosis ensues,” said Dr. Herzog.
Study details
The newly diagnosed patients were older (mean age, 70 years) than the end-stage IPF patients (mean age, 60 years) and patients with IPF and lung cancer (mean age, 64 years; P < .0001).
Among newly diagnosed IPF patients, a receiving operating characteristic analysis before antifibrotic treatment determined a cutoff LMR value of less than 4.18, with an area under the curve of 0.67 (P = .025). Values below 4.18 were associated with shorter survival (hazard ratio, 6.88; P = .027).
Patients with LMR less than 4.18 were more likely to be men (89% vs. 67%; P = .036), had a lower percent predicted forced vital capacity (76% vs. 87%; P = .023), and were more likely to die or undergo lung transplant (34% vs. 5%; P = .009).
Mortality results
A Kaplan-Meier curve illustrated a stark difference between patients with LMR of 4.18 or higher, nearly all of whom remained alive out to almost 100 months of follow-up. Around 30% of those with LMR less than 4.18 remained alive while close to 100% of the patients with LMR below this value showed worsened outcomes. “You don’t normally see curves like that,” said Dr. Herzog.
There was no significant difference in blood cell counts and ratios at the time of IPF diagnosis and after 1 year of antifibrotic treatment, which suggests that the risk profile is independent of treatment, according to the study authors.
Among patient subgroups, those with IPF and lung cancer had the lowest mean LMR (2.2), followed by newly diagnosed patients (3.5), and those with end-stage disease (3.6; P < .0001).
The study authors reported financial relationships with various pharmaceutical companies. Dr. Herzog had no relevant financial disclosures.
A low lymphocyte-to-monocyte ratio (LMR) is associated with worse survival in newly-diagnosed patients with idiopathic pulmonary fibrosis (IPF), according to a new retrospective, single-center analysis. Patients with both IPF and lung cancer also had a lower LMR than patients with IPF alone.
The study, published online in Respiratory Medicine, was conducted among 77 newly diagnosed patients, 40 end-stage IPF patients, and 17 patients with IPF and lung cancer. All received at least 1 year of antifibrotic therapy (pirfenidone or nintedanib). The researchers collected demographic and clinical data between December 2014 and December 2020.
The disease course of IPF is difficult to predict, with some patients progressing slowly, and others suffer a rapid decline to respiratory failure. Previous studies found that higher levels of monocytes are associated with higher mortality in IPF and other fibrotic lung disease, and both neutrophil-to-lymphocyte ratio (NLR) and LMR have been shown to predict mortality in lung cancer.
A previous study found that IPF patients had a higher NLR and a lower LMR than controls, but that research did not consider the impact of antifibrotic treatment, which may improve outcomes.
There has been accumulating cellular and molecular evidence that leukocyte population abnormalities are associated with IPF outcomes, but that work was more discovery based and relied on tests that aren’t readily available clinically, said Erica L. Herzog, MD, PhD, who was asked to comment on the study. “It’s provided a lot of insight into potential new mechanisms and potential biomarkers, but their clinical utility for patients is limited. So the use of lymphocyte-to-monocyte ratios that can be obtained from a complete blood cell count, which is a test that can be done in any hospital, would really be a game-changer in terms of predictive algorithms for patients with IPF,” said Dr. Herzog, who is a professor of medicine and pathology at Yale University, New Haven, Conn., and director of the Yale ILD Center of Excellence.
In humans, abnormalities in circulating monocytes and lymphocytes have individually been linked worse IPF outcomes. Animal studies have implicated monocyte-derived cells in lung fibrosis, but because animal studies have shown that lymphocyte populations are not required for fibrosis, more work is needed.
“I think what we’re finding is that lymphocytes probably have a regulatory role, and there’s probably a protective population and potentially a pathogenic population. Something about the balance between adaptive immunity, which is reflected by your lymphocytes, and innate immunity, which is reflected by your monocytes. Something about that balance is important for tissue homeostasis, and then when it’s disrupted or perturbed, fibrosis ensues,” said Dr. Herzog.
Study details
The newly diagnosed patients were older (mean age, 70 years) than the end-stage IPF patients (mean age, 60 years) and patients with IPF and lung cancer (mean age, 64 years; P < .0001).
Among newly diagnosed IPF patients, a receiving operating characteristic analysis before antifibrotic treatment determined a cutoff LMR value of less than 4.18, with an area under the curve of 0.67 (P = .025). Values below 4.18 were associated with shorter survival (hazard ratio, 6.88; P = .027).
Patients with LMR less than 4.18 were more likely to be men (89% vs. 67%; P = .036), had a lower percent predicted forced vital capacity (76% vs. 87%; P = .023), and were more likely to die or undergo lung transplant (34% vs. 5%; P = .009).
Mortality results
A Kaplan-Meier curve illustrated a stark difference between patients with LMR of 4.18 or higher, nearly all of whom remained alive out to almost 100 months of follow-up. Around 30% of those with LMR less than 4.18 remained alive while close to 100% of the patients with LMR below this value showed worsened outcomes. “You don’t normally see curves like that,” said Dr. Herzog.
There was no significant difference in blood cell counts and ratios at the time of IPF diagnosis and after 1 year of antifibrotic treatment, which suggests that the risk profile is independent of treatment, according to the study authors.
Among patient subgroups, those with IPF and lung cancer had the lowest mean LMR (2.2), followed by newly diagnosed patients (3.5), and those with end-stage disease (3.6; P < .0001).
The study authors reported financial relationships with various pharmaceutical companies. Dr. Herzog had no relevant financial disclosures.
FROM RESPIRATORY MEDICINE