• neurodegeneration
• electronic nose
• cognitive function
• olfaction

The sense of smell is one of the five human senses, whose importance has increased in last decades for scientific and clinical community. Indeed, olfaction was seen as an early biomarker for neurodegeneration and neuroregeneration, as well as for cognitive status, being the olfactory neurons the only neural cells whose regeneration was ascertained in human body.
Thus, the employment of olfactory testing in research and clinical practice is nowadays always more frequent, especially in the most burdensome neurodegenerative conditions, such as Parkinson’s (PD) and Alzheimer’s (AD) Disease, where the link between cognitive decrease, disease progression and smell loss is more evident. A possible interesting add-on to current research knowledge about the link between olfaction and neurodegeneration could be represented by the olfactory assessment in elderly subjects with Mild Cognitive Impairment (MCI), a prodromal dementia possibly resulting in AD or PD within some years. Actually, the link between the two conditions is not clear, with several evidence towards an olfactory decrease even in MCI subjects, even though the studies published lack of methodological completeness.
Concerning neuroregeneration, it is largely known that this phenomenon occurs in various parts of the human body, among which the olfactory bulb, and it is widely accepted that a number of external agents could inhibit adult neurogenesis, including X-rays exposure. It is also known that high-doses of ionizing radiation (IR) exposure are associated, for example, with DNA damage, resulting in a number of conditions, including cancer and cognitive detriment. On the other hand, the effects of low-doses of IR are currently poorly known, being widely influenced by the subjective individual’s response. Among the workers exposed to low-doses of IR, a quite important model is represented by the cohort of invasive cardiologists operating in the cardiac catheterization laboratory, resulting as the most massively exposed among the cohorts of clinicians, thus possibly representing an unique model for the investigation of cognitive effects of low-doses IR exposure.
Nevertheless, olfaction is also influenced by a number of subjective factors, among which, for example, age, gender, smoking, comorbilities, but also by genetics, whose influence was already documented in recent literature studies. The Brain-Derived Neurotrophic Factor (BDNF) represents therefore a possible factor influencing smell ability, being largely associated with neural trafficking, neuron growth and cognitive functioning and, in some instance, with subjective attitude towards neurodegeneration. The association between olfaction and a BDNF polymorphism, Val66Met, was evaluated in elderly subjects, and seen to be associated with their brain aging. However, elderly subjects could display a number of comorbilities that could have accounted for spurious response to olfactory testing, thus this assessment performed in a cohort of young adults could provide a number of useful clean information, less affected by external biases.
One of the possible useful employments of smell assessment is the evaluation of functional anosmia, possibly caused by associated conditions. One of such conditions is represented by Kallmann’s Syndrome (KS), the association of hypogonadotrophic hypogonadism (HH) and anosmia, this latter condition resulting from failed olfactory bulb development. Thus, the evaluation of olfactory function could be of extreme interest in clinical practice, especially in the case of differential diagnosis with respect to other similar conditions not associated with functional anosmia.
A number of literature studies investigated the association between smell and neurodevelopmental disorders, including autism. Nevertheless, the olfactory evaluation in healthy subjects, not affected by the condition but displaying the so-called “autistic features”, like all human beings, associated with the attitude of the brain towards a more empathic or more systemizing behavior, has never been considered to date, and could represent an useful insight into a more precise knowledge of sensory processing in autistic and typical subjects.
The processing of odorous stimuli is, to date, still largely investigated, and one of the most important research topics for scientific community is currently the evaluation of autonomic response to olfactory stimuli. Thus, the evaluation of physiological data, dealing with heart rate, vagal tone, or baroreflex could be interesting to enlighten knowledge in this field.
All the models above stated have been succesfully implemented in this PhD thesis in order to add a noteworthy scientific contribution to the current research trends in this field.
Furthermore, beyond the measurement of olfactory function in human models, we decided to explore the technological side of the sense of smell, represented by systems based on electronic nose.
The E-Nose is a technological system, inspired to the functioning of human nose, employed for the detection and characterization of odorant compounds in several areas of interest, including food industry, environmental monitoring and diagnostics. It is used in complement or alternative to traditional laboratory analysis, such as Gas Chromatography-Mass Spectrometry (GC-MS), when such techniques result particularly obtrusive or of difficult application.
In this thesis, systems based on E-Nose technology are applied to diagnostics, in particular for the support to traditional diagnosis methods for the discrimination of two pulmonary pathologies, namely Primary (PCD) and Secondary Ciliary Dyskinesia (SCD), both characterized by a lower ciliary clearance of mucus and by an abnormal production of Volatile Organic Compounds (VOCs) in exhaled breath, and to environmental monitoring, with such a similar tool implemented and integrated within an Autonomous Underwater Vehicle (AUV) and into a moored buoy for the detection of hydrocarbons on the sea surface of a marine protected area.
Both the systems proposed demonstrated their operability in the fields of interest and could possibly form the future basis for integrated tools for both diagnostics and marine monitoring, respectively.