Breath gas analysis
Encyclopedia
Breath gas analysis is a method for gaining non-invasive information on the clinical state of an individual by monitoring volatile organic compound
s present in the exhaled breath. Breath gas concentration can then be related to blood
concentrations via mathematical modeling as for example in blood alcohol testing.
winner Linus Pauling
demonstrated that human breath is a complex gas, containing more than 200 different volatile organic compounds. However, physicians have used breath analysis since the days of Hippocrates
.
volatile organic compounds (VOCs) are released within the human organism as a result of normal metabolic
activity or due to pathological disorders. They enter the blood stream and are eventually metabolized or excreted via exhalation
, skin
emission, urine
, etc.
Breath sampling is non-invasive and breath samples can be extracted as often as desired.
Identification and quantification of potential disease biomarkers can be seen as the driving force for the analysis of exhaled breath. Moreover, future applications for medical diagnosis and therapy control with dynamic assessments of normal physiological function or pharmacodynamics are intended.
Exogenous
VOCs penetrating the body as a result of environmental exposure can be used to quantify body burden. Also breath tests are often based on the ingestion of isotopically labeled precursors, producing isotopically labeled carbon dioxide
and potentially many other metabolites.
However, breath sampling is far from being a standardized procedure due to the numerous confounding factors biasing the concentrations of volatiles in breath. These factors are related to both the breath sampling protocols as well as the complex physiological mechanisms underlying pulmonary gas exchange. Even under resting conditions exhaled breath concentrations of VOCs can strongly be influenced by specific physiological parameters such as cardiac output and breathing patterns, depending on the physico-chemical properties of the compound under study.
Understanding the influence of all this factors and their control is necessary for achieving an accurate standardization of breath sample collection and for the correct deduction of the corresponding blood concentration levels.
The simplest model relating breath gas concentration to blood concentrations was developed by Farhi
Volatile organic compound
Volatile organic compounds are organic chemicals that have a high vapor pressure at ordinary, room-temperature conditions. Their high vapor pressure results from a low boiling point, which causes large numbers of molecules to evaporate or sublimate from the liquid or solid form of the compound and...
s present in the exhaled breath. Breath gas concentration can then be related to blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
concentrations via mathematical modeling as for example in blood alcohol testing.
History
The area of modern breath testing commenced in 1971, when Nobel PrizeNobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
winner Linus Pauling
Linus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
demonstrated that human breath is a complex gas, containing more than 200 different volatile organic compounds. However, physicians have used breath analysis since the days of Hippocrates
Hippocrates
Hippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...
.
Overview
EndogenousEndogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
volatile organic compounds (VOCs) are released within the human organism as a result of normal metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
activity or due to pathological disorders. They enter the blood stream and are eventually metabolized or excreted via exhalation
Exhalation
Exhalation is the movement of air out of the bronchial tubes, through the airways, to the external environment during breathing....
, skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
emission, urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, etc.
Breath sampling is non-invasive and breath samples can be extracted as often as desired.
Identification and quantification of potential disease biomarkers can be seen as the driving force for the analysis of exhaled breath. Moreover, future applications for medical diagnosis and therapy control with dynamic assessments of normal physiological function or pharmacodynamics are intended.
Exogenous
Exogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....
VOCs penetrating the body as a result of environmental exposure can be used to quantify body burden. Also breath tests are often based on the ingestion of isotopically labeled precursors, producing isotopically labeled carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
and potentially many other metabolites.
However, breath sampling is far from being a standardized procedure due to the numerous confounding factors biasing the concentrations of volatiles in breath. These factors are related to both the breath sampling protocols as well as the complex physiological mechanisms underlying pulmonary gas exchange. Even under resting conditions exhaled breath concentrations of VOCs can strongly be influenced by specific physiological parameters such as cardiac output and breathing patterns, depending on the physico-chemical properties of the compound under study.
Understanding the influence of all this factors and their control is necessary for achieving an accurate standardization of breath sample collection and for the correct deduction of the corresponding blood concentration levels.
The simplest model relating breath gas concentration to blood concentrations was developed by Farhi
-
where
denotes the alveolar concentration which is assumed to be equal to the measured concentration.
It expresses the fact that the concentration of an inert gas in the alveolar air depends on the mixed venous concentration
, the substance-specific blood:air partition coefficient 
, and the ventilation-perfusion ratio 
.
But this model fails when two prototypical substances like acetoneAcetoneAcetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
(partition coefficient
) or isopreneIsopreneIsoprene , or 2-methyl-1,3-butadiene, is a common organic compound with the formula CH2=CCH=CH2. Under standard conditions it is a colorless liquid...
(partition coefficient
) are measured.
E.g., multiplying the proposed population mean of approximately
acetone in end-tidal breath by the partition coefficient 
at body temperature grossly underestimates observed (arterial) blood levels spreading around 
. Furthermore, breath profiles of acetone (and other highly soluble volatile compounds such as 2-pentanone or methyl acetate) associated with moderate workload ergometer challenges of normal healthy volunteers drastically depart from the trend suggested by the equation above.
Hence some more refined models are necessary. Such models have been developed recently.
Applications
Breath gas analysis is used in a number of breath testBreath testA breath test is a type of test performed on air generated from the act of exhalation.Types include:*Breathalyzer - By far the most common usage of this term relates to the legal breath test to determine if a person is driving under the influence of alcohol.*Hydrogen breath test - it is becoming...
s.
- AsthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
detection by exhaled nitric oxideExhaled nitric oxideIn medicine, exhaled nitric oxide can be measured in a breath test for asthma or other conditions characterized by airway inflammation. Nitric oxide is a gaseous molecule produced by certain cell types in an inflammatory response. The fraction of exhaled NO is a promising biomarker for the... - Blood alcohol testing
- Lung cancerLung cancerLung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
detection - Diabetes detection
- Fructose malabsorption with hydrogen breath testHydrogen Breath TestA hydrogen breath test is used as a clinical medical diagnosis for people with irritable bowel syndrome, and common food intolerances. The test is simple, non-invasive, and is performed after a short period of fasting . Even though the test is normally known as a "Hydrogen Breath Test" some...
- Helicobacter pyloriHelicobacter pyloriHelicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
with urea breath testUrea breath testThe urea breath test is a rapid diagnostic procedure used to identify infections by Helicobacter pylori, a spiral bacterium implicated in gastritis, gastric ulcer, and peptic ulcer disease. It is based upon the ability of H. pylori to convert urea to ammonia and carbon dioxide... - Diagnosis of bad breath
- Organ rejection
Analytical instruments
Breath analysis can be done with various forms of mass spectrometry, but there are also simpler methods for specific purposes, such as the HalimeterHalimeterA Halimeter is an instrument for measurement of the level of volatile sulfur compounds in the mouth.Halimeter was introduced in the early 1990s as an adjunct method for determining halitosis levels, alongside human assessment of odor levels...
and the breathalyzerBreathalyzerA breathalyzer or breathalyser is a device for estimating blood alcohol content from a breath sample...
.
- Gas chromatography-mass spectrometry GC-MS
- Proton transfer reaction mass spectrometry PTR-MS and PTR-TOFTime-of-flight mass spectrometryTime-of-flight mass spectrometry is a method of mass spectrometry in which an ion's mass-to-charge ratio is determined via a time measurement. Ions are accelerated by an electric field of known strength. This acceleration results in an ion having the same kinetic energy as any other ion that has...
- Selected ion flow tube mass spectrometry SIFT-MS
- Ion mobility spectrometry IMS
- Fourier transform infrared spectroscopy FTIR
- Laser spectrometry SpectroscopySpectroscopySpectroscopy is the study of the interaction between matter and radiated energy. Historically, spectroscopy originated through the study of visible light dispersed according to its wavelength, e.g., by a prism. Later the concept was expanded greatly to comprise any interaction with radiative...
- Chemical sensors resp. Electronic noseElectronic noseAn electronic nose is a device intended to detect odors or flavors.Over the last decade, “electronic sensing” or “e-sensing” technologies have undergone important developments from a technical and commercial point of view...
External links
- Asthma