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

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

doi:10.1016/j.eclinm.2022.101758

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

EClinicalMedicine. 2022 Dec 1:55:101758. doi: 10.1016/j.eclinm.2022.101758. eCollection 2023 Jan.

Authors

Theresia A Mikolasch^{1

2}, Peter M George^{3

4}, Jagdeep Sahota^{1

2}, Thomas Nancarrow^{5

6}, Shaney L Barratt^{7

8}, Felix A Woodhead^{9

10}, Vasilis Kouranos^{3

4}, Victoria S A Cope³, Andrew W Creamer^{7

8}, Silan Fidan^{9

10}, Balaji Ganeshan¹¹, Luke Hoy¹¹, John A Mackintosh^{3

12}, Robert Shortman¹¹, Anna Duckworth⁶, Janet Fallon¹³, Helen Garthwaite², Melissa Heightman², Huzaifa I Adamali^{7

8}, Sarah Lines⁶, Thida Win¹⁴, Rebecca Wollerton⁶, Elisabetta A Renzoni^{3

4}, Matthew Steward⁶, Athol U Wells^{3

4}, Michael Gibbons⁶, Ashley M Groves¹¹, Bibek Gooptu^{9

10}, Chris J Scotton^{5

6}, Joanna C Porter^{1

2}

Affiliations

¹ CITR, UCL Respiratory, UCL, London, UK.
² Interstitial Lung Disease Service, UCLH NHS Trust, London, UK.
³ Interstitial Lung Disease Unit, Royal Brompton Hospital, UK.
⁴ National Heart and Lung Institute, Imperial College London, UK.
⁵ College of Medicine & Health, University of Exeter, Exeter, UK.
⁶ Academic Department of Respiratory Medicine, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.
⁷ Bristol Interstitial Lung Disease Service, North Bristol NHS Trust, Bristol, UK.
⁸ Academic Respiratory Unit, University of Bristol, Bristol, UK.
⁹ Institute for Lung Health and Leicester Interstitial Lung Disease Service and NIHR Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital, Groby Road, Leicester, LE3, UK.
¹⁰ Department of Respiratory Sciences and Leicester Institute of Structural & Chemical Biology University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester, LE1 5HB, UK.
¹¹ Institute of Nuclear Medicine, UCL and Department of Nuclear Medicine UCLH, UK.
¹² The Prince Charles Hospital, Queensland, Australia.
¹³ Department of Respiratory Medicine, Somerset Lung Centre, Musgrove Park Hospital, Taunton, UK.
¹⁴ Lister Hospital, North East Herts Trust, Stevenage UK.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in IPF.

Methods: We adopted a two-stage discovery (n = 71) and validation (n = 134) design using patients from the UCL partners (UCLp) cohort. We then combined discovery and validation cohorts and included an additional 794 people with IPF, using real-life data from 5 other UK centers, to give a combined cohort of 999 patients. Data were collected from patients presenting over a 13-year period (2006-2019) with mean follow up of 3.7 years (censoring: 2018-2020).

Findings: In the discovery analysis, we showed that high values of NLR (>/ = 2.9 vs < 2.9) were associated with increased risk of mortality in IPF (HR 2.04, 95% CI 1.09-3.81, n = 71, p = 0.025). This was confirmed in the validation (HR 1.91, 95% CI 1.15-3.18, n = 134, p = 0.0114) and combined cohorts (HR 1.65, n = 999, 95% CI 1.39-1.95; p < 0·0001). NLR correlated with GAP stage and GAP index (p < 0.0001). Stratifying patients by NLR category (low/high) showed significant differences in survival for GAP stage 2 (p < 0.0001), however not for GAP stage 1 or 3. In a multivariate analysis, a high NLR was an independent predictor of mortality/progression after adjustment for individual GAP components and steroid/anti-fibrotic use (p < 0·03). Furthermore, incorporation of baseline NLR in a modified GAP-stage/index, GAP-index/stage-plus, refined prognostic ability as measured by concordance (C)-index.

Interpretation: We have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines cohort staging with GAP. NLR may allow timely prioritisation of at-risk patients, even in the absence of lung function.

Funding: Breathing Matters, GSK, CF Trust, BLF-Asthma, MRC, NIHR Alpha-1 Foundation.

Keywords: Biomarker; ILD; IPF; Interstitial Lung Disease; Leukocyte; Mortality.

Abstract

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