Plasma biomarkers of progressive idiopathic pulmonary fibrosis (IPF) may be markers of progressive pulmonary fibrosis regardless of the type of interstitial lung disease (ILD), according to study results published in American Journal of Respiratory and Critical Care Medicine.
IPF, chronic hypersensitivity pneumonitis (CHP), connective tissue disease-associated ILD (CTD-ILD), and unclassifiable ILD (U-ILD) are the most common forms of ILD that often result in pulmonary fibrosis. A number of circulating plasma biomarkers have been linked to varying survival rates in patients with IPF, but the way these biomarkers affect other ILD subtypes is unknown. The objective of this study was to test and confirm whether increased concentration of certain biomarkers would predict reduced survival in patients with ILD subtypes other than IPF.
Researchers evaluated patients diagnosed with CTD-ILD (n=148), CHP (n=98), or U-ILD (n=159) who consented to a research blood draw. Blood samples were collected between May 2016 and December 2018 at the University of California-Davis and from between March 2010 and August 2016 at the University of Chicago.
Researchers determined the concentration of plasma biomarkers CXCL13, CA-125, MMP7, YKL-40, SP-D, and VCAM-1 using a Luminex® magnetic bead-based custom multiplex assay. The primary end point was 2-year progression-free survival defined as mortality, lung transplant, or ≥10% relative decline in forced vital capacity. Lung function was similar among all participants, although age, gender, race, and immunosuppressive exposure between each ILD subtype varied significantly.
Results revealed that in each ILD subtype, reduced survival was associated with increased concentration of all biomarkers, with the exception of SP-D in the CTD-ILD group. Increased CXCL13 predicted reduced survival in all 3 ILD subtypes, while MMP7, CA-125, and VCAM-1 predicted reduced survival in only CHP and U-ILD. In CTD-ILD, survival association for the plasma biomarker CXCL13 was (hazard ratio [HR], 4.44; 95% CI, 2.0-9.84; P <.001); in CHP, survival association for CXCL13 was (HR, 2.08; 95% CI, 1.11-3.92; P =.023); and in U-ILD, survival association for CXCL13 was (HR, 2.69; 95% CI, 1.36-5.30; P =.004).
This study had 3 limitations. First, sample sizes were relatively small to result in underpowered biomarker analyses. Second, findings may have been influenced by varying plasma storage times between centers. Third, the researchers could not determine biomarker threshold precision given the multiplex platform used in this study.
The researchers concluded that molecular markers of progressive IPF may be markers of progressive pulmonary fibrosis regardless of ILD subtype, although more research may be needed to validate findings and determine how these biomarkers can have an effect on making clinical decisions in all types of ILD.
Alqalyoobi S, Adegunsoye A, Linderholm A, et al. Circulating plasma biomarkers of progressive interstitial lung disease [published online September 16, 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201907-1343LE