Preliminary Analysis: Breath Biopsy® Discovery of Biomarkers for ILA and IPF

Preliminary Analysis: Breath Biopsy® Discovery of Biomarkers for ILA and IPF

Luisa Quesada*1, Jose Manuel Martinez Manzano*1, Yichen Chen*2, Jason Cooper2, Jason Kinchen2, Planchart Ferretto1, Maria Angelica1, Cheryl Nickerson-Nutter3, Marc Van der Schee$2, Ivan Rosas$1

*Equal contribution to lead authorship;

$Equal contribution to senior authorship;

1 Brigham And Women's Hospital, 75 Francis Street, Boston, MA 02115, 617-732-5500, USA;

2 Owlstone Medical, 183 Cambridge Science Park, Milton Road, Cambridge CB4 0GJ, UK;

3 Three Lakes Foundation, Northbrook, Illinois,USA

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Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease associated with progressive and irreversible fibrosis of the lung parenchyma. Interstitial lung abnormalities (ILA) have been postulated as an early-stage imaging finding of pulmonary fibrosis. IPF and ILA are thought to produce unique volatile organic compounds (VOCs) detectable on breath that could be applied as diagnostic biomarkers. This study aims to identify new VOC biomarkers for Control, ILA and IPF groups.

Subjects with IPF, ILA and controls were enrolled at Brigham and Women's Hospital, Boston, MA and breath samples were collected, before and after a six minute walk (SMWT), using the ReCIVA® Breath Sampler, before analysis with thermal desorption gas chromatography mass spectrometry (TD-GC-MS). 29 distinct molecular features (MFs) were detected, of which 22 MFs were shown to differ (unadjusted P<0.05*) between IPF patients and controls, pre SMWT. In contrast, 27 MFs showed evidence of difference post-SMWT test, 3 of which are robust predictors of controls vs. IPF in multivariate analysis. Most of the MFs that showed a statistically significant difference in IPF vs. control also showed a similar trend in ILA vs. control.

12 MFs showed evidence of difference between ILA and IPF, pre-SMWT. Importantly, each of these molecules showed opposite associations between IPF vs control and ILA vs control, likely reflecting biological mechanisms that are more different between IPF and ILA than between IPF/ILA and controls. These MFs showed potential as predicters of which ILA subjects might develop IPF. When compared with clinical variables, 4 MFs showed robust capacity to predict defusing capacity for carbon monoxide (DLCO). Based on these results it may be possible to predict some ILA subjects to be more likely to develop IPF than others. The study was limited due to small ILA group size, the next step would be a separate validation study.





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