Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosis

Mikolasch, Theresia; George, Peter M.; Sahota, Jagdeep; Nancarrow, T; Barratt, Shaney; Woodhead, Felix; Kouranos, Vasilis; Cope, Victoria S A; Creamer, Andrew; Fidan, Silan; Ganeshan, Balaji; Hoy, Luke; Mackintosh, John A.; Shortman, Robert I.; Duckworth, Anna; Fallon, Janet; Garthwaite, Helen; Heightman, Melissa; Adamali, Huzaifa; Lines, Sarah; Win, Thida; Wollerton, Rebecca; Renzoni, Elisabetta; Steward, Matthew; Wells, Adrian; Gibbons, Michael; Groves, Ashley M.; Gooptu, Bibek; Scotton, Chris J.; Porter, Joanna C.

doi:10.1016/j.eclinm.2022.101758

“…The trend of lower lymphocytes count with progression of fibrosis mirrors the findings of previous studies 5 36. Lymphocytic aggregates are a recognised pathological feature of IPF lesions 27 37.…”

Section: Discussionsupporting

confidence: 83%

“…Blood monocyte levels also correlated with the extent of fibrosis on CT scan,3 and Kreuter et al also found an association with a composite measure of IPF outcome (forced vital capacity (FVC) decline, 6 min walk distance reduction, acute exacerbation and/or mortality) 4. Moreover, we (and others) have shown that the neutrophil:lymphocyte ratio (NLR) is also a predictor of mortality and FVC decline,5 6 and patients with higher levels of neutrophils were more likely to progress from indeterminate for Usual Interstitial Pneumonia (UIP) CT pattern to UIP pattern and a clinical diagnosis of IPF 7…”

Section: Introductionsupporting

confidence: 60%

Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study

Achaiah,

Fraser,

Saunders

et al. 2023

BMJ Open Resp Res

2

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Clinical studies have demonstrated association between different blood leucocytes and mortality and forced vital capacity (FVC) decline. Here, we question which blood leucocyte levels are specifically associated with progression of fibrosis, measured by accumulation of fibrosis on CT scan using a standardised automated method.MethodsUsing the Computer-Aided Lung Informatics for Pathology Evaluation and Rating CT algorithm, we determined the correlation between different blood leucocytes (<4 months from CT) and total lung fibrosis (TLF) scores, pulmonary vessel volume (PVV), FVC% and transfer factor of lung for carbon monoxide% at baseline (n=171) and with progression of fibrosis (n=71), the latter using multivariate Cox regression.ResultsNeutrophils (but not monocyte or lymphocytes) correlated with extent of lung fibrosis (TLF/litre) (r=0.208, p=0.007), PVV (r=0.259, p=0.001), FVC% (r=−0.127, p=0.029) at baseline. For the 71 cases with repeat CT; median interval between CTs was 25.9 (16.8–39.9) months. Neutrophil but not monocyte levels are associated with increase in TLF/litre (HR 2.66, 95% CI 1.35 to 5.25, p=0.005).ConclusionOur study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.

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“…2 Blood monocyte levels also correlated with the extent of fibrosis on CT scan, 3 and Kreuter also found an association with a composite measure of IPF outcome (FVC decline, 6-minute-walk distance reduction, acute exacerbation and/or mortality). 4 Moreover, we and others found that the neutrophil:lymphocyte ratio is also a predictor of mortality and FVC decline, 5,6 and patients with higher levels of neutrophils were more likely to progress from indeterminate for UIP CT pattern to UIP pattern and a clinical diagnosis of IPF. 7…”

Section: Introductionmentioning

confidence: 73%

“…The trend of lower lymphocytes count with progression of fibrosis mirrors the findings of previous studies. 5,36 Lymphocytic aggregates are a recognised pathologic feature of IPF lesions. 27,37 The association between low blood lymphocyte count and adverse outcomes in IPF is currently unknown but could be explained in part by lymphocyte dysfunction, 38 and the sequestering of lymphocytes into sites of inflammation, such as the fibrotic lung.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study

Achaiah,

Fraser,

Saunders

et al. 2023

Preprint

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Clinical studies have demonstrated association between different blood leukocytes and mortality and FVC decline. Here we question which blood leukocyte levels are specifically associated with progression of fibrosis, measured by accumulation of fibrosis on CT scan using a standardised automated method.MethodsUsing the CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) CT algorithm, we determined the correlation between different blood leukocytes (<4 months from CT) and total lung fibrosis (TLF) scores, pulmonary vessel volume (PVV), FVC% and TLCO% at baseline (n=171) and with progression of fibrosis (n=71), the latter using multivariate Cox regression.ResultsNeutrophils (but not monocyte or lymphocytes) correlated with extent of lung fibrosis (TLF/litre) (r=0.208, p=0.007), PVV (r=0.259, p=0.001), FVC% (r=-0.127, p=0.029) at baseline. For the 71 cases with repeat CT; median interval between CTs was 25.9 (16.8-39.9) months. Neutrophil but not monocyte levels are associated with increase in TLF/litre [HR 2.66, 95%CI, 1.35-5.25, p=0.005].ConclusionOur study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.Key messagesWHAT IS ALREADY KNOWN ON THIS TOPICIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic condition. Recently, several human studies have implicated blood leukocyte levels (monocyte, neutrophil and lymphocyte) with FVC decline and mortality. However, direct association between leukocytes and progression of fibrosis using quantitative CT analysis has not been explored.WHAT THIS STUDY ADDSThis study explored the association between blood monocytes, neutrophils and lymphocytes against increase in fibrosis over time, measured using a quantitative CT algorithm, CALIPER. We show that levels of blood neutrophil and lymphocytes but not monocytes were associated with greater risk of progression of fibrosis.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE AND/OR POLICYOur study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.

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“…Peripheral monocyte (Mo) counts were positively correlated with fibrotic lesions on chest CT 6. Furthermore, peripheral Mo counts and NLR are associated with disease progression and all-cause mortality in patients with IPF 7–11…”

Section: Introductionmentioning

confidence: 99%

Neutrophil–lymphocyte ratio in patients with idiopathic pleuroparenchymal fibroelastosis

Suzuki,

Kono,

Hasegawa

et al. 2023

BMJ Open Resp Res

3

0

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BackgroundIdiopathic pleuroparenchymal fibroelastosis (iPPFE), a progressive fibrotic disease, is characterised by upper lobe–dominant lung fibrosis involving the pleura and subpleural lung parenchyma. However, no prognostic markers have been established for this condition. Associations between blood leucocyte levels and mortality have been reported in patients with idiopathic pulmonary fibrosis; therefore, we hypothesised that peripheral leucocyte levels are associated with mortality risk in patients with iPPFE.MethodsThis retrospective study longitudinally assessed peripheral leucocyte counts at the time of diagnosis and 1 year after diagnosis in two cohorts of 127 patients with iPPFE (69 and 58 patients in Seirei and Hamamatsu cohorts, respectively).ResultsA comprehensive assessment of peripheral leucocytes revealed that the neutrophil–lymphocyte ratio (NLR) was associated with mortality in patients with iPPFE after adjusting for age, sex and forced vital capacity in multivariate analyses (adjusted HR, 1.131; 95% CI, 1.032 to 1.227). When the patients were classified based on the median NLR, those with a high NLR had shorter survival than those with a low NLR (median, 32.2 vs 79.8 months; HR, 2.270; 95% CI, 1.416 to 3.696). Interestingly, the results of the NLR classification by median were longitudinally preserved in >70% of patients, and patients with consistently high NLR were at a higher risk of mortality than others (median, 24.8 vs 79.6 months; HR, 3.079; 95% CI, 1.878 to 5.031). Compared with the gender–age–physiology model, a composite model comprising age, sex and NLR could successfully stratify patients with iPPFE into three groups according to mortality risk.ConclusionThe assessment of peripheral leucocyte counts is easy and might be useful in evaluating disease severity and mortality risk in patients with iPPFE. Our study suggests the importance of focusing on peripheral leucocyte levels in daily practice.

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Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosis

Cited by 17 publications

References 45 publications

Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study

Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study

Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study

Neutrophil–lymphocyte ratio in patients with idiopathic pleuroparenchymal fibroelastosis

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