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The widely available neutrophil-to-lymphocyte ratio test proved effective in predicting survival in idiopathic pulmonary fibrosis and helped improve use of the Gender-Age-Physiology (GAP) Index for staging, an observational study of almost 1000 patients in the United Kingdom found.
Reporting online in The Lancet, pilocarpine model of epilepsy the UK investigators found that neutrophil-to-lymphocyte ratio (NLR) ≥ 2.9 correlated with a twofold increased risk of death in IPF (hazard ratio [HR] 2.04; 95% CI, 1.09-3.81; P = .025) in a derivation cohort of IPF patients (n = 71) enrolled at the University College London Hospital (UCLH) from 2008 to 2018.
“While we do know that NLR is predictive of poor outcomes in a variety of diseases, we were interested to see whether or not there’s any evidence it has predictive value in idiopathic pulmonary fibrosis and would it show that an elevated NLR does indeed mean that these patients have poorer survival compared to people with low NLR,” lead author Theresia A. Mikolasch, MBChB, a respiratory consultant at Cambridge University Hospitals, told Medscape Medical News. “That was replicated across several big IPF centers within the UK.” Mikolasch conducted the research when she was at University College London, London, England.
The observational study then used additional cohorts, including a validation cohort for NLR (n = 134) from UCLH enrolled from 2006 to 2018 and external cohorts (n = 794) from five other centers in the UK, to further evaluate the primary finding, which was confirmed with HRs of 1.91 (95% CI, 1.15-3.18; P = .0114) in the validation cohort and 1.65 (95% CI, 1.39-1.95; P < .0001) in the combined cohorts (n = 999).
“The main attractiveness of the NLR test is that it’s so easy,” Mikolasch said. “Everybody gets full blood count, and it seems to add value in trying to stratify which patients might need earlier attention.”
The study also found that NLR correlated with the GAP stage and GAP Index (P < .0001). When the study stratified patients from low to high based on NLR results, it found significant differences in survival for GAP stage 2 (P < .0001), but not for GAP stage 1 or 3.
NLR and other biomarkers may be helpful in stratifying patients on a population-based approach, Mikolasch said. “But how well do they actually work for the individual? You will find that some people with high NLR go on and live for 10 years and you will find people with low NLR who die earlier. It’s all part of the clinical jigsaw puzzle.”
But NLR has the potential to improve risk stratification in clinical trials of IPF patients, Mikolasch said. “You might want to risk stratify according to lung function and then additionally look at factors like NLR, which would be quite easy to do.”
The rationale for the study was based on previous evidence that high neutrophil counts had been associated with poor survival in IPF and other lung diseases, Mikolasch said, including 2016 research from Turkey that reported the association in scleroderma.
The utility of NLR is that it can be used in resource-poor settings and by family physicians, Mikolasch said. “You can sort out the patients with high NLR, give them extra attention, start antifibrotics earlier, and be much more vigilant about possible exacerbations.”
She acknowledged criticisms of NLR, mainly that it may not differentiate IPF survival from heart disease or other comorbidities a patient may have. “It is quite blunt, but it does correlate with lung function,” she said of the test. “Even if it’s not perfect and it’s not the most elegant, it’s so simple and it’s so cheap, why don’t you just use it?”
Mikolasch cautioned that these findings may not be readily applicable in the United States because of the UK’s nationalized healthcare system. She added that the study did not account for ethnicity, which may also make the findings less meaningful in ethnically diverse countries like the United States.
The study was funded by Breathing Matters, GlaxoSmithKline, Cystic Fibrosis Trust, BLF-Asthma (Asthma + Lung UK), Medical Research Council, National Institute for Health and Care Research, and Alpha-1 Foundation. Mikolasch reported no relevant financial relationships.
Lancet. Published online December 1, 2022. Full Text.
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