Neutrophil lymphocyte ratio as an indicator for disease progression in Idiopathic Pulmonary Fibrosis

Abstract

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease. Patients present at different stages and disease course is varied. Blood monocytes have been linked to all-cause mortality, and neutrophils to progression to IPF in patients with the indeterminate for usual interstitial pneumonia CT pattern.

Objective: To determine association between blood monocytes, neutrophils and lymphocytes levels (and their derived indexes), with lung function decline and mortality in IPF.

Methods: We performed a retrospective analysis of an IPF cohort (n=128) who had their first clinical visit at the Oxford Interstitial Lung Disease Service between 2013 and 2017. Association between blood monocytes, neutrophils, lymphocytes and derived indexes (within 4 months of visit) and decline in forced vital capacity (FVC) and all-cause mortality were assessed using Cox proportional hazard regression analysis. Kaplan-Meier analysis was used to assess time-to-event for 10% FVC decline and mortality for patients dichotomised to high and low leucocyte counts.

Results: Median length of follow-up was 31.0 months (IQR 16.2-42.4); 41.4% demonstrated FVC decline >10% per year and 43.8% died. In multivariate models (incorporating age, gender and initial FVC%), raised neutrophils, lymphopaenia and neutrophil:lymphocyte ratio were associated with FVC decline (p≤0.01); while both monocytes and neutrophil levels (and their derived indexes) were associated with all-cause mortality (p≤0.01). Kaplan-Meier analysis also showed association between neutrophils and its derived indexes but not monocyte, with FVC decline.

Conclusion: Blood neutrophil and lymphopaenia are more sensitive than monocytes as prognostic indicators of disease progression in those with established IPF.

Keywords: innate immunity; interstitial fibrosis; neutrophil biology.

Figure 1

Flow diagram of radiographic progression of UIP within the IPF cohort (n=230). *Clinical diagnosis as per 2011 IPF guideline and as per 2018 IPF guideline. ATLS, Latin American Thoracic Society; ATS, American Thoracic Society; ERS, European Respiratory Society; IPF, Idiopathic pulmonary fibrosis; JRS, Japanese Respiratory Society; UIP, usual interstitial pneumonia.

Figure 2

Alluvial plots demonstrating the proportion of patients per clincal outcome measure. (A) Illustrates the proportions of cases demonstrating stable and progressive radiological appearance in patients that underwent follow-on CT scan (n=86). (B) Illustrates the proportion of cases with disease progression (either on follow-on CT and/or by demonstrating FVC >10% decline/year), hospitalisation events and survival. FVC, forced vital capacity; UIP, usual interstitial pneumonia.

Figure 3

Kaplan-Meier curves for FVC decline dichotomised by normal and abnormal upper limit for leucocytes and by median values for the derived indexes of monocyte:lymphocyte ratio (MLR) (>0.37), neutrophil:lymphocyte ratio (NLR) (>2.77) and Systemic Inflammatory Response Index (SIRI) (>2.00). P value calculated with log rank test. P value calculated with log rank test. FVC, forced vital capacity.

Figure 4

Kaplan-Meier curves for survival dichotomised by normal and abnormal upper limit for leucocytes and by median values for the derived indexes of monocyte:lymphocyte ratio (MLR) (>0.37), neutrophil:lymphocyte ratio (NLR) (>2.77) and Systemic Inflammatory Response Index (SIRI) (>2.00). P value calculated with log rank test.