Preface Free

Since antiquity, physicians have learned to evaluate their patients through body smells among them odors from breath, urine, feces and skin. Nowadays, the old disciplines continue to provide vital information, but smell is becoming so universal that researchers are sometimes overzealous in asking for many more than may be needed from the regular clinical chemistry and application in real-world conditions. This makes the very clear point that it is best to have some focus with respect to chemical compounds composing smell, and the investigator needs to know which ones may be most relevant to a disease for which the diagnosis is uncertain.

During the last decades, it has been evidenced that smell of a disease is tightly linked with “volatile biomarkers”, commonly expressed via volatile organic compounds (VOCs), viz. small molecules that have high vapor pressure. These molecules tend to stand out as individuals or profiles in body fluids or cells, offering a means of comparing the physiology of the human body under different circumstances such as in growth, imbalance and disease. In pathophysiological cases, the presence of certain volatile molecules can indicate that a strong response is being mounted to some insult, injury, infection or infestation. Knowing that biomarkers before symptoms appear or when there is no overt symptomology is important in diagnosis, since prevention is better than cure, and early detection invariably gives a better prognosis. This is exemplified where the progression of a disease could be rapid and fatal, as can occur in certain types of cancer. The more specific a volatile biomarker is for a particular state, the more useful it becomes. But if the volatile markers are little more than indicators of the possibility that a particular condition or state prevails, the more different ones that can be demonstrated, the better the interpretation.

Today the search for volatile biomarkers for all kinds of diseases and disorders is as intensive as ever, with new technologies making it even more probable for help in the medical care of all kinds of disease. This includes the case in drug development, where the efficacy of a novel compound can be tested to see whether it has any impact of some marker(s) being expressed under a diseased condition. Amid this gold rush to discover new volatile biomarkers in the present day of bioinformatics, the link between the target and cellular physiology has been largely forgotten. Step by step, there is an increasing arduous effort in finding how all these volatile molecules interact and integrate to reflect information storage and expression platforms on the “factory floor”. At the working end of each cell that makes up the tissues and body of an organism, even the smallest change in the open nonequilibrium system can influence the whole of the cell and human body.

Given the huge range of enzymes, fats, peptides, structural proteins, polyamine, saccharides, nucleic acids, hormones, cofactors etc. within a cell, volatilomics (i.e., the scientific study of chemical processes involving profiles of VOCs) clearly have their place in modern human health. By concentrating on only the small molecules intimately tied up in the machinery, volatilomics clearly relies on the most up-to-date and sophisticated analyses, with demands for every sort of analytical (mostly spectroscopic) machines that have large capacities for identifying and quantifying chemicals at reasonable levels of detection that are now technically possible. Profiles of compounds will get bigger and bigger as further developments in technology lead to greater sensitivity, so that volatilomes (VOCs that originate from an organism, super-organism or ecysystem) at ppb or sub-ppb levels can be detected and quantified.

The spread of interest in biomarkers as technological advances took place and showed the wide range of variations in human beings in disorders – always based on hypothetical “norms”. With ever increasing data combined with years of experience in making accurate and preferably direct correlations with diseased states, these practices have made and will increasingly make a huge impact on the general medical care of patients. In their early days, these elaborated machines were expensive, and at first few computers were available with the appropriate software to handle the data. Modern technology will soon be bringing us to the point where volatilomics, with the use of special sensor array analyses and other combinations of analytical procedures and machine learning algorithms, will have an increasingly powerful role to play in medicine, and computers will be able to handle and help us “mine” vast arrays of information, against an ever growing human volatilomics database.

This book comprises chapters written by scientific authorities in particular areas of volatile biomarkers in human health. Some of the chapters are focused on disciplinary topics, and others are more inter- and multidisciplinary in nature. The book introduces the key role and advantages that volatile biomarkers play in the expression of the (bio)chemistry of the human body, as well as in communication between biological cells living as individual entities or as mini societies that sense, respond and adapt to changes in their environment. The book starts with an ensemble of chapters focusing on the origin, emission, expression and mechanistic pathways of volatile biomarkers into the blood, from which they can be secreted into most body fluids (blood, breath, skin, urine, saliva, feces etc.). The book continues, via its second part, with the role and utility of VOCs as signaling agents between various cells, between cells and organism communities and between cells and key body parts, such as the immune system. This is followed by the third part of the book, which aims at engineering VOC expressions by combining VOC interplays in various body fluids, as well as by adapting volatile biomarker properties, to obtain improved performances in disease diagnosis and monitoring. The fourth part of the book focuses on the appraisal and translation of the accumulating knowledge from the laboratory to the point-of-care phase, starting from sampling and using spectrometry and other spectroscopic techniques for analytical identification and classifications of the VOCs and ending with the use of selective sensors as well as desktop and wearable artificial sensing devices, e.g., electronic noses and electronic skins, in conjugation with AI-assisted data processing and healthcare decision making in diagnostics. Signal analysis and data treatment via machine learning and AI algorithms are described throughout the fifth chapter, a topic that is more and more being realized as critical to volatile biomarker analysis. The book ends with offering an outlook into the challenges in the continuing development of volatile biomarkers and their wider availability to healthcare, which can be substantially improved.

Hossam Haick