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

Abstract

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