Exhalative Breath Markers Do Not Offer for Diagnosis of Interstitial Lung Diseases: Data from the European IPF Registry (eurIPFreg) and Biobank

Abstract

Background: New biomarkers are urgently needed to facilitate diagnosis in Interstitial Lung Diseases (ILD), thus reducing the need for invasive procedures, and to enable tailoring and monitoring of medical treatment. Methods: In this study we investigated if patients with idiopathic pulmonary fibrosis (IPF; n = 21), non-IPF ILDs (n = 57) and other lung diseases (chronic obstructive pulmonary disease (COPD) n = 24, lung cancer (LC) n = 16) as well as healthy subjects (n = 20) show relevant differences in exhaled NO (FeNO; Niox MINO), or in eicosanoid (PGE2, 8-isoprostane; enzyme-linked immunosorbent assay (ELISA)) levels as measured in exhaled breath condensates (EBC) and bronchoalveolar lavage fluids (BALF). Results: There was no significant difference in FeNO values between IPF, non-IPF ILDs and healthy subjects, although some individual patients showed highly elevated FeNO. On the basis of the FeNO signal, it was neither possible to differentiate between the kind of disease nor to detect exacerbations. In addition, there was no correlation between FeNO values and lung function. The investigation of the eicosanoids in EBCs was challenging (PGE2) or unreliable (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 (HP) and sarcoidosis, possibly indicating severity of oxidative stress. Conclusions: FeNO-measurements are not of diagnostic benefit in different ILDs including IPF. The same holds true for PGE2 and 8-isoprostane in EBC by ELISA.

Exhaled Biomarkers in Idiopathic Pulmonary Fibrosis—A Six-Month Follow-up Study in Patients Treated with Pirfenidone

“…Despite higher serum and EBC TSLP levels in IPF patients when compared to controls in that study, the concentrations of TSLP in these two materials did not correlate [20]. Krauss et al also did not find relationships between EBC and BALF concentrations of PGE2 and 8-isoprostane in patients with different interstitial lung diseases, including IPF [25]. Therefore, we believe that cytokine level measurements in serum, BALF and sputum should not be extrapolated to EBC in patients with IPF.…”

“…Although a previous report showed that EBC analysis might modestly contribute to the diagnosis and monitoring of IPF [25], some authors demonstrated that EBC composition might discriminate between IPF patients and control subjects [20,26]. It seems that these equivocal findings may result from the complex cytokine interplay in the pathogenesis of IPF and a (still) insufficient knowledge of the specific cytokines involved.…”

Exploring the Ability of Electronic Nose Technology to Recognize Interstitial Lung Diseases (ILD) by Non-Invasive Breath Screening of Exhaled Volatile Compounds (VOC): A Pilot Study from the European IPF Registry (eurIPFreg) and Biobank

“…In some cases, e.g., IPF, the patient’s survival might be still limited despite novel antifibrotic therapies [7,8]. Although significant progress in the understanding of the pathogenesis of ILDs has been made, the natural course, progression factors, biomarkers, and the response to the treatment of an individual patient still cannot be reliably predicted [9,10,11].…”

Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review

“…The potential value of eNO in the differential diagnosis of IPF is surely intriguing, but still largely unexplored. Few studies have been specifically designed to investigate the potential value of eNO parameters in the differential diagnosis of ILDs [ 7 , 8 , 51 , 55 ]. Among these, the papers by Oishi et al and Cameli et al were the only ones to implement multiple-flows eNO assessment in their studies.…”

“…Therefore, FeNO appears not to be reliable for the evaluation of NO production, and generally of inflammatory processes involving distal airways or alveolar spaces. Accordingly, conflicting results has been published concerning the significance of FeNO in respiratory diseases characterized by a more prominent involvement of peripheral districts, such as chronic obstructive pulmonary disease (COPD) or interstitial lung diseases (ILD) [ 5 , 6 , 7 , 8 ]. In order to overcome these limits, the extended analysis of FeNO, able to discriminate between bronchial and alveolar origins of eNO, have been repeatedly reported in the last decade, till the last technical standard document by ERS officially endorsed this procedure for future research [ 9 ].…”