Breathomics to diagnose systemic sclerosis using thermal desorption and comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry.
Delphine ZanellaJulien GuiotPierre-Hugues StefanutoLaurie GiltayMonique HenketFrançoise GuissardBéatrice AndréMichel MalaiseJudith PotjewijdFlorence SchleichRenaud LouisJean-François FocantPublished in: Analytical and bioanalytical chemistry (2021)
Systemic sclerosis is a rare autoimmune disease associated with rapidly evolving interstitial lung disease, responsible for the disease severity and mortality. Specific biomarkers enabling the early diagnosis and prognosis associated with the disease progression are highly needed. Volatile organic compounds in exhaled breath are widely available and non-invasive and have the potential to reflect metabolic processes occurring within the body. Comprehensive two-dimensional gas chromatography coupled to high-resolution mass spectrometry was used to investigate the potential of exhaled breath to diagnose systemic sclerosis. The exhaled breath of 32 patients and 30 healthy subjects was analyzed. The high resolving power of this approach enabled the detection of 356 compounds in the breath of systemic sclerosis patients, which was characterized by an increase of mainly terpenoids and hydrocarbons. In addition, the use of 4 complementary statistical approaches (two-tailed equal variance t-test, fold change, partial least squares discriminant analysis, and random forest) resulted in the identification of 16 compounds that can be used to discriminate systemic sclerosis patients from healthy subjects. Receiver operating curves were generated that provided an accuracy of 90%, a sensitivity of 92%, and a specificity of 89%. The chemical identification of eight compounds predictive of systemic sclerosis was validated using commercially available standards. The analytical variations together with the volatile composition of room air were carefully monitored during the timeframe of the study to ensure the robustness of the technique. This study represents the first reported evaluation of exhaled breath analysis for systemic sclerosis diagnosis and provides surrogate markers for such disease.
Keyphrases
- systemic sclerosis
- interstitial lung disease
- gas chromatography
- end stage renal disease
- newly diagnosed
- high resolution mass spectrometry
- high resolution
- chronic kidney disease
- ejection fraction
- mass spectrometry
- rheumatoid arthritis
- type diabetes
- prognostic factors
- tandem mass spectrometry
- peritoneal dialysis
- risk assessment
- cardiovascular disease
- idiopathic pulmonary fibrosis
- liquid chromatography
- risk factors