Breath biomarkers in idiopathic pulmonary fibrosis: a systematic review

Abstract

BackgroundExhaled biomarkers may be related to disease processes in idiopathic pulmonary fibrosis (IPF) however their clinical role remains unclear. We performed a systematic review to investigate whether breath biomarkers discriminate between patients with IPF and healthy controls. We also assessed correlation with lung function, ability to distinguish diagnostic subgroups and change in response to treatment.MethodsMEDLINE, EMBASE and Web of Science databases were searched. Study selection was limited to adults with a diagnosis of IPF as per international guidelines.ResultsOf 1014 studies screened, fourteen fulfilled selection criteria and included 257 IPF patients. Twenty individual biomarkers discriminated between IPF and controls and four showed correlation with lung function. Meta-analysis of three studies indicated mean (± SD) alveolar nitric oxide (CalvNO) levels were significantly higher in IPF (8.5 ± 5.5 ppb) than controls (4.4 ± 2.2 ppb). Markers of oxidative stress in exhaled breath condensate, such as hydrogen peroxide and 8-isoprostane, were also discriminatory. Two breathomic studies have isolated discriminative compounds using mass spectrometry. There was a lack of studies assessing relevant treatment and none assessed differences in diagnostic subgroups.ConclusionsEvidence suggests CalvNO is higher in IPF, although studies were limited by small sample size. Further breathomic work may identify biomarkers with diagnostic and prognostic potential.Electronic supplementary materialThe online version of this article (10.1186/s12931-019-0971-8) contains supplementary material, which is available to authorized users.

Alveolar concentration of nitric oxide as a prognostic biomarker in idiopathic pulmonary fibrosis

“…The correlation between CaNO and TLCO% may result both by an impairment of alveolar diffusion and by the increase of NO production at alveolar levels, as demonstrated by Pullamssetti [20]. The reliability of CaNO were confirmed by a recent metanalysis in which CaNO emerged as the most promising of various breath biomarkers for clinical management of IPF [21].…”

The use of exhaled air analysis in discriminating interstitial lung diseases: a pilot study

“…Consequently, there is still a need for discriminative breathomics to diagnose and monitor ILDs. Until now, only two of such comprehensive breathomic studies have examined the excretion of disease-specific VOCs in ILDs [ 79 ]. In the first study in 2005, elevated level of ethane were reported to be exhaled in the breath of 34 ILD patients compared to the exhaled air of 16 healthy controls [ 80 ].…”

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

“…Biomarker research has been undertaken using peripheral blood, bronchoalveolar lavage fluid (BALF), and exhaled breath condensate (EBC) [11]. Numerous molecules involved in alveolar epithelial cell injury, proliferation and matrix remodeling as well as immune regulation have been proposed as potential biomarkers [10].…”