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

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.
Competing Interests: SLB reports consultancy fees from Boehringer Ingelheim (BI). PMG reports personal fees from BI and AstraZeneca (AZ) and Brainomix and lecturing honoraria from BI, Roche and Cipla. VK reports lecturing fees from Novartis, Roche, and BI. JCP reports consulting fees from Carrick therapeutics, AZ and lecturing honaria from The Limbic. EAR reports lecturing fees from BI and Mundipharma. SL reports conference attendance support from BI. AUW reports honoraria from BI and Roche and consulting fees from Roche, BI and Veracyte. FAW reports support for conference attendance from BI. FW is now a full-time employee of Avalyn Pharma Inc, but all work related to this manuscript was carried out whilst a fulltime NHS employee of the University Hospitals of Leicester NHS Trust. All other authors have nothing to disclose.
(© 2022 The Authors.)