Electronic Nose and Exhaled Breath NMR-based Metabolomics Applications in Airways Disease

Abstract

Breathomics, the multidimensional molecular analysis of exhaled breath, includes analysis of exhaled breath with gas-chromatography/mass spectrometry (GC/MS) and electronic noses (e-noses), and metabolomics of exhaled breath condensate (EBC), a non-invasive technique which provides information on the composition of airway lining fluid, generally by high-resolution nuclear magnetic resonance (NMR) spectroscopy or MS methods. Metabolomics is the identification and quantification of small molecular weight metabolites in a biofluid. Specific profiles of volatile compounds in exhaled breath and metabolites in EBC (breathprints) are potentially useful surrogate markers of inflammatory respiratory diseases. Electronic noses (e-noses) are artificial sensor systems, usually consisting of chemical cross-reactive sensor arrays for characterization of patterns of breath volatile compounds, and algorithms for breathprints classification. E-noses are handheld, portable, and provide real-time data. E-nose breathprints can reflect respiratory inflammation. E-noses and NMR-based metabolomics of EBC can distinguish patients with respiratory diseases such as asthma, COPD, and lung cancer, or diseases with a clinically relevant respiratory component including cystic fibrosis and primary ciliary dyskinesia, and healthy individuals. Breathomics has also been reported to identify patients affected by different types of respiratory diseases. Patterns of breath volatile compounds detected by e-nose and EBC metabolic profiles have been associated with asthma phenotypes. In combination with other -omics platforms, breathomics might provide a molecular approach to respiratory disease phenotyping and a molecular basis to tailored pharmacotherapeutic strategies. Breathomics might also contribute to identify new surrogate markers of respiratory inflammation, thus, facilitating drug discovery. Validation in newly recruited, prospective independent cohorts is essential for development of e-nose and EBC NMRbased metabolomics techniques.

Recent Advances in NMR-Based Metabolomics

“…11 Airway diseases have also been investigated based on the NMR analysis of exhaled breadth condensate (EBC). 12 The potential of NMR-based metabolomics of EBC, known as breathomics, as well as electronic noses based on other diagnostic platforms in distinguishing patients with respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, cystic fibrosis, or primary ciliary dyskinesia associated with the respiratory system are discussed. One major hypothesis related to the development of obesity is related to intestinal microbiota, apart from lifestyle habits and genetic factors.…”

Identifying biomarkers for asthma diagnosis using targeted metabolomics approaches

“…Of the twelve articles identified in our focused review, seven performed metabolomics analysis in exhaled breath condensate [22–28], two in urine [29,30], one in bronchoalveolar lavage fluid [31], one in plasma [32], and one in serum [33]. Five used nuclear magnetic resonance spectroscopy [22,24,28,29,33], three used liquid chromatography-mass spectrometry [27,30,32], three used gas chromatography-mass spectrometry [23,25,26], and one used both gas and liquid chromatography [31].…”

CFTR modulator therapies in pediatric cystic fibrosis: focus on ivacaftor

“…The study of exhaled breath from CF patients is a valuable and noninvasive tool; beyond FENO, other breathomics tools applicable to CF include electronic noses, nuclear magnetic resonance (NMR) spectroscopy, and gas-chromatography/mass spectrometry [87]. NMR spectroscopy of exhaled breath condensate has been shown to discriminate CF patients from healthy controls, CF patients from patients with primary ciliary dyskinesia, and stable (no clinical or FEV 1 change from baseline in the last 4 weeks) from unstable CF patients [88, 89].…”