Plasma levels of 2 oxidative stress markers, advanced glycosylated end-products (AGE) and advanced oxidation protein products (AOPP), were significantly higher in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy individuals, researchers found.

In addition, AGE levels distinguished between IPF and connective tissue disease-associated interstitial lung disease (CTD-ILD). This finding disclosed a potential role for AGE in aiding differential diagnosis.

“Due to the similar morphological, clinical, and radiological characteristics of IPF and CTD-ILD, accurate differential diagnoses at earlier stages are especially important, given the therapeutic and prognostic implications,” the researchers wrote in the study, published in the Journal of Clinical Medicine.

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The analysis of receiver operating characteristic (ROC) curves showed that AOPP (area under the curve [AUC], 0.80, 95% CI, 0.63-0 .98, P <.001) and AGE (AUC, 0.78, 95% CI, 0.60-0.97, P <.001) allowed for the distinction between IPF patients (n=29, age, 63.3 ± 2.7 years, 65.5% male) and healthy controls (n=30, age, 58.3 ± 3.5 years, 60% male).

The authors reported a 69.2% specificity and 83.3% sensitivity for AOPP, using a cut-off value of 202.5 µM, while AGE presented 80% specificity and 71.4% sensitivity, considering a cut-off value of 2370 arbitrary units (AU).

Moreover, IPF patients had lower (P <.03) plasma concentrations of AGE when compared to CTD-ILD patients (n=14, age, 60 ± 2.9 years, 42.9% male).

Cabrera et al also determined the levels of circulating matrix metalloproteinase 7 (MMP7), a promising prognostic biomarker for IPF in other studies. Accordingly, in this study, MMP7 exhibited the highest sensitivity (92.3%) and specificity (92.9%) to diagnose IPF. The study authors showed that MMP7 levels distinguished between IPF patients and healthy controls (AUC, 0.96, 95% CI, 0.91-1, P <.001), using a cut-off value of 2.07 ng/mL.

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The study cohort was recruited from the Interstitial Lung Disease Unit at Virgen de la Victoria University Hospital in Malaga, Spain. IPF and CTD-ILD patients received anti-fibrotic and immunosuppressive treatments, respectively.

IPF and CTD-ILD are examples of interstitial lung diseases, a large group of lung disorders that usually cause inflammation and scarring in the lungs.


Cabrera Cesar E, Lopez-Lopez L, Lara E, et al. Serum biomarkers in differential diagnosis of idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease. J Clin Med. 2021;10(14):3167. doi:10.3390/jcm10143167