Exhalative Breath Biomarkers Not Useful to Distinguish Among Different ILDs, Study Reports

Measuring three specific biomarkers — nitric oxide, PGE2, and 8‐isoprostane — in the exhaled breath condensates (EBC) or bronchoalveolar lavage fluids (BALF) of patients with different forms of interstitial lung disease or other lung diseases does not show diagnostic potential, a study suggests.

The study, “Exhalative Breath Markers Do Not Offer for Diagnosis of Interstitial Lung Diseases: Data from the European IPF Registry (eurIPFreg) and Biobank,” was published in the Journal of Clinical Medicine.

Interstitial lung disease (ILD) is an umbrella term that includes more than 200 lung disorders, which largely overlap in terms of clinical features and appearance on imaging tests. Telling them apart is often impossible without performing an invasive test such as a biopsy. Consequently, new biomarkers are urgently needed to assist in the diagnosis of ILDs, and enable proper treatment.

In the study, data from the European IPF registry (eurIPFreg) and eurIPFbank were analyzed. Specifically, the researchers compared the levels of fraction exhaled nitric oxide (FeNO), prostaglandin E2 (PGE2), and 8-isoprostane in the EBC or BALF of patients with different forms of ILD, other lung diseases, and healthy people used as controls.

In total, the team analyzed samples from 21 patients with idiopathic pulmonary fibrosis (IPF), 57 patients with ILDs not caused by IPF, 24 with chronic obstructive pulmonary disease (COPD), and 16 with lung cancer, as well as 20 healthy people.

Nitric oxide (NO) is a gaseous molecule produced by certain cell types during an inflammatory response. It is considered an oxidative stress marker, and can be easily measured in a breath test. 8-Isoprostane, a prostaglandin, is also a marker of oxidative stress, which is implicated in the the development of fibrosis.

PGE2 is a known antifibrotic mediator that plays an important role in wound resolution.

Researchers found no significant differences in FeNO values among IPF, non‐IPF ILDs, and healthy participants, although some individual patients showed highly elevated FeNO levels. The results showed that based on FeNO levels, it was not possible to differentiate between the kind of disease nor to detect disease exacerbations. In addition, there was no correlation between FeNO values and lung function.

Investigation of the other two biomarkers in EBCs was challenging, namely for PGE2, or unreliable, in the case of 8‐isoprostane, but worked out well in BALF. A significant increase of free 8‐isoprostane was observed in BALF, but not in EBCs, of patients with IPF, hypersensitivity pneumonitis, and sarcoidosis, possibly indicating the severity of oxidative stress.

Based on the results, the team concluded that none of the potential biomarkers tested had diagnostic value for the different ILDs.

“No significant and meaningful difference in the FeNO, PGE2, or 8‐isoprostane values in EBC or BALF could be observed between different forms of ILD’s, especially IPF, and other lung diseases such as COPD or [lung cancer] and healthy controls,” the researchers wrote.

“Our results do not support previous studies in IPF patients and other ILDs, according to which NO is an important marker for the assessment of disease severity. To our understanding, FeNO or PGE2 or 8‐isoprostane measurements in BALF do not offer as diagnostic or prognostic markers, nor do they indicate exacerbation,” they concluded.

Further research on potential biomarkers to distinguish among ILDs is therefore still needed.