Inflammation

In 2012, Richards et al. published a study that analyzed 92 potential biomarkers in an initial cohort of 140 patients with IPF. They followed this with validation in an independent cohort of 101 additional patients with IPF. The authors then developed and tested an integrated risk prediction score using a combination of protein markers and patient characteristics. 

The authors found that high concentrations of ICAM-1 predicted poor overall survival, poor transplant-free survival, and poor progression-free survival in the initial patient cohort. In the independent validation cohort, the results were comparable: high concentrations of ICAM-1 predicted poor transplant-free survival, poor overall survival, and poor progression-free survival.

In 2014, Vuga et al. published the results of a study that measured CXCL13 in the lungs and blood plasma of samples taken from patients with IPF. The authors set out to determine if CXCL13, which mediates B-cell trafficking and is associated with many antibody-mediated conditions, is also associated with IPF progression.

The authors found that IPF lungs contained eight times more CXCL13 than normal lungs. Plasma CXCL13 concentrations were highest in samples from IPF patients, compared to those from normal lungs. IPF patients with the highest CXCL13 levels had significantly lower six-month survival rates, and CXCL13 increases of more than 50% from baseline levels predicted respiratory failure. 

In 2018, Neighbors et al. published a post-hoc analysis of the test and replication cohorts from the CAPACITY 004, CAPACITY 006, and ASCEND phase III clinical trials of pirfenidone. For this analysis, the authors were interested in the predictive and prognostic qualities of 12 biomarkers in IPF, one of which was CCL18.

Of the 12 baseline biomarkers several, including CCL18, were prognostic for progression outcomes in the placebo groups of the test cohort. However, only CCL18 was consistently prognostic for absolute change in percentage of predicted forced vital capacity (FVC) in both patient cohorts. Blood CCL18 concentrations were the most consistent predictor of disease progression across IPF cohorts.