Blood Levels of Molecules May Distinguish IPF From Other ILDs

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Measuring the levels of certain molecules in the blood could be useful for distinguishing idiopathic pulmonary fibrosis (IPF) from other types of lung disease, according to a recent study.

The study, “Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease,” was published in the Journal of Clinical Medicine

IPF, a chronic disorder that causes lung tissue scarring, or fibrosis, without a clear underlying cause, is one of the most common types of interstitial lung disease (ILD) — a group of disorders characterized by lung fibrosis.

Another ILD form, called connective tissue disease-associated interstitial lung disease (CTD-ILD), can arise in people with diseases that affect connective tissues, such as scleroderma or lupus. (Connective tissues are those that support and protect other tissues and organs in the body.)

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Both IPF and CTD-ILD can have similar clinical presentation, but their treatments differ. For this reason, a differential diagnosis — the process physicians follow to assess whether an individual has one disease or the other — is crucial.

A team of scientists in Spain tested whether measuring the levels of several molecules in the blood could aid in the differential diagnosis of IPF and CTD-ILD.

Specifically, researchers focused on measuring the levels of advanced glycosylated end-products (AGE) and advanced oxidation protein products (AOPP). These molecules are associated with inflammation and oxidative stress — a type of cell damage caused by high levels of oxidant molecules — and may be promising ILD biomarkers.

They also measured the levels of matrix metalloproteinase 7 (MMP7), an established IPF biomarker.

Blood levels of AGE, AOPP, and MMP7 were measured in samples from 73 individuals recruited at a hospital in Malaga, Spain: 29 with IPF, 14 with CTD-ILD, and 30 healthy volunteers. All groups were similar demographically by age (about 60) and sex, and most either former or active smokers.

Researchers found the levels of all three biomarkers were significantly higher among individuals with IPF or CTD-ILD, compared with healthy controls. Between patient groups, AGE levels were significantly higher in the blood of those with CTD-ILD than those with IPF.

“Our data show serum levels of all markers in IPF or CTD-ILD patients that are significantly higher than those in healthy participants. Moreover, AGE was also significantly elevated in CTD-ILD compared with the IPF group,” the researchers wrote.

No statistically significant differences were seen in other markers between these two patient groups, though “the levels of MMP7 were more elevated in CTD-ILD patients than in the IPF group, and, conversely, AOPP levels were more elevated in IPF patients than in the CTD-ILD group,” the team noted.

Investigators then used statistical tests to explore the diagnostic utility of these biomarkers. A measure called the area under the receiver operating curve, or AUC, showed that all three markers could be used to distinguish ILD patients from healthy volunteers with a fairly high degree of accuracy.

The highest AUC values — reflecting greater accuracy — were obtained for MMP7, indicating that this marker is more strongly associated with disease.

“Our results provide support for the potential value of serum AGE, AOPP, and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD, with MMP7 being one of the most valuable biomarkers for differentiating between ILD patients and healthy controls,” the researchers wrote.

The team then calculated the sensitivity and specificity of using these biomarkers to differentiate between IPF and CTD-ILD. Of note, sensitivity is a test’s ability to correctly identify individuals with a disease (true positives), while specificity is its ability to correctly identify individuals without the disorder (true negatives).

Using AGE and MMP7 in combination resulted in a sensitivity of 93.33% and a specificity of 100% for differentiating between these two forms of ILD, the team found.

While MMP7 is a well-established IPF biomarker, “this study demonstrates, for the first time, the possible use of AGE as a differential diagnostic biomarker between IPF and CTD-ILD,” the researchers wrote.

They noted their study was limited by its small size, its cross-sectional design, and the fact that it was carried out at a single institution.

“Undoubtedly, multi-centre and prospective studies are necessary to understand the role of AGE in IPF and CTD-ILD differential diagnosis,” they wrote.

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