Table 1 Summary of characteristics and results of all included studies with reference to primary and secondary review questions. aDecliners defined as drop on FVC of ≥10% or DLCO ≥ 15% in preceding 6–12 months. All studies were case-control study design except for Ono (2008 and Kotecha (2016) which were uncontrolled cohort studies
From: Breath biomarkers in idiopathic pulmonary fibrosis: a systematic review
Reference | Country | Biomarkers of interest | Sample Medium | Analytical method | IPF (n) | Healthy controls (n) | Primary Question – IPF vs healthy controls | Secondary Question – Lung function correlation | Secondary Question – treated vs untreated |
|---|---|---|---|---|---|---|---|---|---|
[58] | Greece | 8-isoprostane, H202 | EBC | EIA, Enzyme assay | 16 | 15 | 8-isoprostane and H202 higher in IPF group. | Negative correlation with DLCO% for both H202 and 8-isoprostane. | Not reported |
[65] | USA | Non-targeted VOCs | Exhaled breath | Colorimetric sensing | 15 | 21 | Sensitivity for IPF group 40.0%, Specificity 92.3%. | Not reported | Not reported |
[67] | Japan | CysLTs, FeNO50 | EBC, Exhaled breath | EIA, Online chemiluminescence analyser | 14 | 0 | Not reported | No correlation between CysLTs and lung function parameters. | Not reported |
[59] | Italy | Metallic elements | EBC | ICP-MS | 19 | 33 | Ni, Cr, Si higher in IPF group. Co, Fe, Cu, Se, Mo lower in IPF group. | No correlation between metallic elements and lung function parameters | No difference in metallic elements based on treatment received |
[60] | Czech | Nitrite, Nitrate | EBC | LC with fluorescence detection | 13 | 29 | Nitrite levels higher in IPF group. Nitrate levels lower in IPF group | Not reported | Not reported |
[55] | Japan | FeNO50, CalvNO, JawNO, 42 Cytokines | Exhaled breath EBC | Online chemiluminescence analyser, Human cytokine antibody assay | 13 | 10 | No difference in FeNO50, CalvNO, JawNO or cytokines. | Not reported | Not reported |
[61] | Italy | MDA | EBC | HPLC with fluorescence detection | 38 | 14 | No difference in MDA levels. | Not reported | Not reported |
[56] | China | CalvNO, JawNO | Exhaled breath | Online chemiluminescence analyser | 14 | 12 | CalvNO higher in IPF group. No difference in JawNO. | Not reported | Not reported |
[62] | Japan | 8-isoprostane | EBC | EIA | 6 | 6 | 8-isoprostane levels higher in IPF group. | Not reported | Not reported |
[63] | USA | Total LPA and sub-species | EBC | LC-MS | 11 | 11 | No difference in Total LPA. 22:4 LPA higher in IPF group. | No correlation between 22:4 LPA and lung function parameters. Total LPA not reported | Not reported |
[57] | Italy | FeNO50, FeNO100, FeNO150, CalvNO | Exhaled breath | Online electrochemical analyser | 32 | 30 | FeNO50–150 and CalvNO higher in the IPF group. | Not reported | Not reported |
[68] | UK | CalvNO | Exhaled breath | Online chemiluminescence analyser | 27 [Stable (n = 16) vs Declinersa(n = 9)] | 0 | Not reported | CalvNO higher in decliners than stable patients. | No difference in CalvNO in treated vs untreated groups. |
[64] | Switzerland | Non-targeted metabolomics | EBC | UHPLC-HRMS | 10 | 10 | One consistent discriminative metabolite (unidentifiable). Higher in IPF patients than controls. | Not reported | Not reported |
[66] | Japan | Non-targeted VOCs | Exhaled breath | MCC-IMS | 40 | 55 | 5 discriminative VOCs; p-cymene, acetoin, isoprene, ethylbenzene and an unidentified VOC. P-cymene was lower in IPF while the rest are higher. | P-cymene showed negative correlation with VC, %VC, FVC, %FVC, DLCO, %DLCO. | Not reported |