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

Abstract

RationaleIdiopathic 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.ObjectiveTo determine association between blood monocytes, neutrophils and lymphocytes levels (and their derived indexes), with lung function decline and mortality in IPF.MethodsWe 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.ResultsMedian 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.ConclusionBlood neutrophil and lymphopaenia are more sensitive than monocytes as prognostic indicators of disease progression in those with established IPF.

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

“…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…”

“…4,21 Our findings suggest that neutrophils may be a contributor to active accumulation of fibrosis in IPF, supported by previous findings of high neutrophils in bronchoalveolar lavage (BAL) of IPF patients, 22 and more recent findings of higher neutrophil:lymphocyte ratio in IPF patients with greater rates of FVC decline. 5…”

“…Neutrophil:lymphocyte ratio (NLR), monocyte:lymphocyte ratio (MLR) and systemic inflammation response index (SIRI)(neutrophil ×monocyte/lymphocyte) were calculated as described previously. 5…”

Identification of immune biomarkers associated with basement membranes in idiopathic pulmonary fibrosis and their pan-cancer analysis

“…On the one hand, inhibition of neutrophil chemokine CXCL8 or lack of neutrophil elastase can reduce bleomycininduced pulmonary fibrosis (Gregory et al, 2015;Gschwandtner et al, 2017). Similarly, increased neutrophils are associated with decreased FVC and all-cause mortality in IPF patients (Achaiah et al, 2022). It has been reported that deletion of exon 18 of COL17A1 in mice leads to IL-17-related inflammatory responses in the skin and infiltration of eosinophils, neutrophils, T-cell and mast cells (Lindgren et al, 2023).…”

The role of neutrophils in the pathogenesis of IPF

“…In a cohort of 156 patients with IPF, a high percentage of BALF neutrophils was an independent predictor of early mortality [ 8 ]. Recently published data have shown that blood neutrophilia is associated with a decline in forced vital capacity and all-cause mortality in IPF [ 9 ], and with progression to IPF in patients with an indeterminate computed tomography pattern for UIP [ 10 ].…”