# Breath Analysis: A Promising Tool for Disease Diagnosis--The Role of Sensors
###### Abstract
Oxidative stress, lipid peroxidation, and reactions catalyzed by cytochrome p450 (CYP450), and liver enzymes are the main biochemical processes correlated with endogenous VOCs [15; 18; 19]. The correlation of oxidative stress and airway inflammation with exhaled VOCs is summarized in Figure 1. Different VOC classes are potentially correlated with different biochemical reactions and exogenous sources. VOCs of exhaled breath are regarded as normal [12]. However, concentration differences for some exhaled VOCs could potentially be associated with an abnormal condition of the body [12], as the metabolic processes producing the VOCs are altered in a distinctive way by different diseases [1; 10]. Disease-related concentration alternations conventionally concern a group of VOCs rather than a single compound [17]. Apart from this, the concentration of a single compound may vary due to more than one pathophysiological processes, thus being non-specific [20]. Consequently, diagnosis of complex, heterogeneous diseases is scarcely achieved by the recognition of one characteristic stand-alone VOC [7; 20]. A mixture of exhaled VOCs, called VOC pattern or 'breathprint', consists the signature of a specific disease, correlating with the underlying pathophysiology; this pattern should therefore be recognized so as to achieve disease diagnosis [7; 17; 20]. Thus, the analysis of the exhaled breath holds a great promise for non-invasive early disease diagnosis [1; 21]. Several diseases are investigated via breath analysis [7] for potential diagnosis, the main types of which are presented on Table 1. Specifically in the case of infections by specific species or strains of bacteria, the combination of bacteria-derived VOCs [22] and VOCs produced by the host due to immune response to bacterial antigens as well as VOCs formed due to the host response to bacterial products/metabolites (and vice versa) is detected. Differentiation of the origin of those VOCs is not clinically important [23]. Recently, research interest focused on the diagnosis of SARS-CoV-2 viral infection via breath analysis with remarkable results [24; 25; 26], employing a diagnostic test, i.e., \"BreFence GoCOVID-19 Breathonix (2017) developed by Breathonix Breathonix (2017) and \"TracieX Breathalyser\" developed by Silver Factory Technology, which have been already provisionally approved by the HSA (2018, 2019). Apart from early diagnosis, screening of high-risk populations and assessment of therapy efficiency can be permitted using breath analysis, due to being an inexpensive (2018) and rapid method, characterized by increased patient compliance (2019). For the analysis of exhaled VOCs and disease diagnosis, two different methods can be used; analytical techniques and sensors. Gas chromatography combined with mass spectrometry (GC-MS) comprises the gold-standard method for the analysis of VOCs patterns in exhaled breath (2018, 2019; 2020). Both quantitative analysis (characterized by high sensitivity in the ppb to ppt range (2018)) and qualitative analysis (providing information concerning the potential metabolic disease pathways (2020)) can be achieved (2018, 2019). For the detection of very low concentrations of VOCs, the pre-concentration of the breath sample is imperative. Pre-concentration techniques commonly combined with GC-MS include thermal desorption (2019, 2020) (using sampling bags/sorbent tubes (2020), mainly Ten