ORIGINAL ARTICLE   

Minerva Respiratory Medicine 2021 September;60(3):73-86

DOI: 10.23736/S2784-8477.21.01933-7

Copyright © 2021 EDIZIONI MINERVA MEDICA

language: English

Biomarkers for possible early detection and progression of idiopathic pulmonary fibrosis

Francesco CAVALLI ¹ ✉, Ermanno PUXEDDU ^{1, 2}, Elisa TEODORI ¹, Maurizia SFORZA ¹, Patrizia DE MARCO ¹, Paola ROGLIANI ^{1, 2}

¹ Division of Respiratory Medicine, Tor Vergata University, Rome, Italy; ² Department of Experimental Medicine, Tor Vergata University, Rome, Italy

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, primarily occurring in older adults, and limited to the lungs. Data on the predictive value of serum and bronchoalveolar lavage (BAL) biomarkers in IPF are limited. The aim of the present study was to evaluate the possible role in IPF of three biomarkers, Carbohydrate Antigen CA 15.3 (CA 15-3), β2-microglobulin (β2m) and D-dimer, as indicators for early diagnosis and disease progression.
METHODS: A single center observational, retrospective study (December 2016 and September 2019), was conducted in a cohort of 100 patients with new diagnosis of IPF. The reference values used to define a serum sample positivity were respectively: >23.50 U/mL for CA 15.3, >0.26 mg/dL for β2m and > 500.00 ng/mL for D-dimer. Forced vital capacity (FVC), carbon monoxide diffusion capacity (DLCO) and the six-minute walking distance (6MWD) were assessed at baseline and at 6 and 12 months after diagnosis. The data were analyzed by Student’s t-test and ANOVA.
RESULTS: The mean serum levels of CA 15.3, β2m and D-dimer resulted higher than the reference limit values, respectively: 46.53±36.6 U/mL for CA 15.3, 0.28±0.08 mg/dL for β2m and 548.3±364.0 ng/mL for D-dimer. At diagnosis, elevated serum levels of CA 15.3, β2m and D-dimer were significantly correlated with a reduced lung function, assessed through the measurement of forced vital capacity (FVC) and total lung capacity (TLC), a reduction of DLCO, a decrease in 6MWD and with more rapid progression of disease. A minimal clinically important difference (MCID) was reached regarding FVC decline at 12 months, between patients with D-dimer elevated at diagnosis, and on average, a 12 months DLCO reduction ≥15% was demonstrated among patients with β2M and D-dimer elevated to diagnosis.
CONCLUSIONS: At diagnosis, patients with altered values of CA 15-3, β2M and D-dimer appear to be older, more symptomatic, with a more defined and compromised pattern of pathology; moreover, they present a more rapid progression of IPF, in the time interval ranging from 6 to 12 months.

KEY WORDS: Antigens, tumor-associated, carbohydrate; Fibrin fragment D; Idiopathic pulmonary fibrosis; Vital capacity; Carbon monoxide