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https://doi.org/10.29013/AJT-20-1.2-47-51
Raimkulova Charos A., Assistant, Department of Chemistry, Samarkand State Medical Institute Aronbaev Sergey D., D. Sc., professor, Department of Chemistry, Samarkand State University Vasina Svetlana M., Ph.D., Associate Professor, Department of Chemistry,
Samarkand State University Aronbaev Dmitry M., Ph.D., Associate Professor, Department of Chemistry,
Samarkand State University Samarkand, University Boulevard E-mail: diron51@mail.ru
EXHALED AIR AS AN OBJECT OF STUDYING THE FUNCTIONAL STATE OF THE ORGANISM
Abstract. The article substantiates the use of an analysis of the composition of exhaled air to assess the physiological state of the human organism. The mechanisms of the appearance of the main biomarkers for various diseases and instrumental methods for their registration are described. It is concluded that the diagnosis of the pathophysiological state of the organism by exhaled air is non-invasive, simple and aesthetic, which, when the hardware and display methods are improved, can become no less informative than the analysis of blood or its serum, tissues and other biological substances.
Keywords: biomarkers, expired air, non-invasive methods, condition diagnosis.
1. Introduction weight inorganic and organic compounds: nitrogen
The development of modern medicine is based oxides [3; 4], ammonia [5], methane and other low
on the improvement of clinical diagnostic methods molecular weight hydrocarbons [6], acetone [7],
with the wide involvement of chemical analysis, glucose, organic acids, neurotransmitters - dopa-methods and devices that allow for the express and mine, catecholamine, high molecular weight organic
minimally, or generally non-invasive method of bio- compounds specific peptides [8].
material sampling, in order to detect markers specific The aim of this work is to substantiate the choice
to this type of disease [1]. In the context of analyti- of air exhaled by a person as an object for non-inva-
cal chemistry, biomarkers should be understood as sive diagnosis of diseases.
changes in the profiles of certain substances recorded 2. Discussion
in chemical biological means by means of chemical It is known that the gas exchange of living organ-analysis [2]. Such markers can be low molecular isms with the environment, in the simplest model of
which is the absorption of oxygen and the release of carbon dioxide and water vapor, is the main factor in their existence and is directly related to their energy consumption [9]. The intensity of the processes is so great that changes in the concentration of O2 and CO2 due to external respiration reach 3-5% or more of the total composition of exhaled air. Other light gases present in the exhale that are formed in the body at concentrations of 10-4-10-6% can be such markers [10].
We consider it appropriate to consider the effect of gases, which are potential biomarkers, on the functional state of the body.
Carbon dioxide CO2. Under normal conditions, the composition of the inhaled air contains about 21% oxygen and 0.03% carbon dioxide, and the exhaled air contains 16% and 4.5%, respectively. Comparison of the normal and pathological state of the organism shows that the content of carbon dioxide in the blood in the amount of 6-8% promotes the absorption of oxygen by the body. With a further increase in its absorption of oxygen begins to decline. With insufficient concentration of carbon dioxide in the blood, oxygen binds excessively firmly to hemoglobin and can no longer "tear itself away" from red blood cells at the right time. And as a consequence of this, the penetration of oxygen into the cells of tissues from the blood decreases several times. Cells begin to experience significant oxygen deficiency with high blood oxygen saturation.
Carbon monoxide CO is a highly toxic gas. When it enters the organism, it binds to hemoglobin contained in red blood cells, with the formation of carboxyhemoglobin COHb. This bright red compound is chemically stable and, when formed, hemoglobin cannot combine with oxygen.
Under normal conditions, endogenous carbon monoxide is formed in the body in small amounts (0.42 ± 0.07) ml / h. At the same time, the physiological norm of COHb concentration is 0.5-1.5%, while in heavy smokers and patients with severe hemolytic anemia and porphyria, it can reach 10%.
Particularly required is monitoring the CO concentration during anesthesia on a half-closed circuit, as this can complicate the elimination of CO from the body with its subsequent accumulation. Signs of carbon monoxide intoxication can be observed when the concentration of this gas in the respiratory circuit rises at a rate of 600-900 ppm/hour. An increase in CO concentration of more than 1.500 ppm/hour is a threat to the patient's life.
Nitric oxide NO. It is generally accepted that nitric oxide, like carbon monoxide, refers exclusively to endogenously formed gases with toxic effects. At the same time, it plays an important role in the life of the organism, as it is associated with a wide variety of biochemical and physiological processes that occur in a living organism. This should especially be attributed to cellular metabolism, since all, without exception, intracellular signals are mediated by secondary bioregulators, which to a large extent include nitric oxide (II). It is proved that through NO the blood vessel expansion mechanism is realized, which means that nitric oxide, as an exhaled gas, reflects the state of the respiratory tract.
It is assumed that the presence of NO in some nerve endings is associated with its participation in the implementation of pain and memory perception mechanisms. Nitric oxide, one way or another, is involved in the implementation of the reactions of the inflammatory cascade, the mechanisms of cell death. So far, the only direct method for determining NO in tissues is gas chromatography. However, it should be taken into account that the usual concentration of nitric oxide in the atmosphere is in the concentration range of 0.4-1.0 ^g/m3, and in the air of industrial cities, and even more so near chemical plants producing nitric acid and nitrogen-containing fertilizers, these values can be exceeded thousands of times, while the change in the concentration of nitrogen oxides in exhaled air in the pathological condition of the patient is only at the level of tens of ppb.
Acetone C3H6O. Acetone is considered a product of the metabolism of free fatty acids. Prolonged
fasting and decompensated diabetes mellitus are those factors in which there is an increased formation of acetone in the body. A small part of the acetone that enters the organism turns into carbon monoxide, which is released with exhaled air. A certain amount of acetone is removed from the organism without changes with exhaled air and through the skin, creating the so-called faint smell of "maple syrup", and some with urine. In the pathological state of the organism, the concentration of acetone in exhaled air can lie in the range of 4-20 ppm.
Ethanol С2Н5ОН. Ethyl alcohol, or ethanol, has pharmacological and toxic effects on the nervous and other systems of the organism. The complexity of the physiological effect of alcohol on the organism, the polymorphism of the clinical manifestations and behavioral actions of the patient, sometimes makes it difficult to accurately measure the vapor of ethyl alcohol in exhaled air. Usually, the concentration of ethanol vapor in exhaled air is expressed in mg/m3 and, taking into account the ratio ofblood density and air, can
be roughly expressed in ppm by blood. At the same time, 0.1 deg./00 of alcohol in the blood corresponds to ~ 45 mg/m3 of alcohol in exhaled air. The ratio of the concentration ofalcohol in the blood and alveolar air is constant, it is determined by the difference in the density of the media: blood and air and averages 1: 2200 with fluctuations from 1300 to 3000. This means that 2200 cm3 of alveolar air contains the same amount of alcohol as in 1 cm3 of blood.
The table 1 shows biomarker substances and their possible presence in the composition of exhaled air during pathological conditions of the organism.
As you can see, the trace gas trace gas in exhaled air is in extremely low concentrations, at ppb level, and the analysis of such trace gas can be based solely on the use of ultra-sensitive equipment and methods, such as mass spectrometry [11], gas chromatography [12-15] spectrophotometry of giant Raman scattering [16] and other, that is, instruments and methods operating on purely physical effects [17-19].
Table 1. - Diseases and associated gases expiratory markers
Diseases Marker gas Concentration
Helicobacter pylori infection; the passage of food through the gastrointestinal tract; liver dysfunction, including cirrhosis; excessive growth of bacteria; pancreatic dysfunction; bile metabolism; glucose metabolism. Carbon dioxide CO2 > 4%
Anemia (hemolytic, sideroblastic, sickle cell); hematomas, hemoglobinuria, infections; respiratory tract infection; asthma. Carbon monoxide (CO) > 2%
Chronic obstructive pulmonary disease; asthma; upper respiratory tract infection; rhinitis; inflammatory processes in the stomach (gastritis), including Helicobacter pylori infection; digestive cancer; severe sepsis; chronic infectious inflammatory processes (gastritis, hepatitis, colitis) Nitric oxide NO 10-100 ppb
Pancreas function in acute destructive pancreatitis and dietary imbalance; severe heart failure; lung cancer. Acetone C3H6O 4-20 ppm
Diseases of the central nervous system; diabetes; alcoholism. Methanol Ethanol Acetaldehyde > 500 ppm 4-20 ppm
Renal failure: with nephritis, hypertension, renal artery atherosclerosis, toxicosis, toxic kidney damage; liver failure with jaundice, hepatitis, cirrhosis, toxic hepatitis; lung cancer. Ammonia NH3 > 1 ppm
Gastrointestinal disorders Methane CH 4 > 5%
As you can see, the trace gas trace gas in exhaled air is in extremely low concentrations, at ppb level, and the analysis of such trace gas can be based solely on the use of ultra-sensitive equipment and methods, such as mass spectrometry [11], gas chromatography [12-15] spectrophotometry of giant Raman scattering [16] and other, that is, instruments and methods operating on purely physical effects [17-19].
However, one should not discount chemical methods that allow concentration of trace micro-
impurities and carry out chemical "amplification" using catalytic and enzymatic reactions [20; 21]. For all this, the diagnosis of the pathophysiological state of the body by exhaled air is non-invasive, simple and aesthetic, which, with the improvement of the hardware design and display methods, can become no less informative than the analysis of blood or its serum, tissues and other biological substances [22-26].
References:
1. Zenkevich I., Volkov V., Avilova I., Kalambet YU., Kalabin G., Savel'eva E., CHernyshev V., SHaj dullina G. Rol' himicheskogo analiza v sovremennoj medicine // Analitika.2017.- No. 1(32). [ in Russian].
2. Zolotov Y. U. A. Himicheskim analiz i medicina // Z. Hurn. analit. himii.2014.- T. 69. - No. 4.- P. 359362. [in Russian].
3. Markov H. M. Oksid azota i oksid ugleroda-novyj klass signal'nyh molekul // Uspekhi fiziologicheskih nauk.1996.- No. 4.- P. 30-43[in Russian].
4. Pat. 2143689. R. F., MPKG01. - No. 33/497. Sposob opredeleniya sostoyaniya serdechno-sosudistoj i dyhatel'noj sistem na osnove analiza oksida azota v vydyhaemom vozduhe / Malyshev I. Y. U. Manuhi-na E. B.- Byul. 1999. - No. 36. [in Russian].
5. Patent 2184781 RF. Sposob diagnostiki helikobakterioza po ocenke ureaznoj aktivnosti biologicheskogo materiala i ustrojstvo dlya ego osushchestvleniya / Dmitrienko M. A., Kornienko E. A., Milejko V. E.-No. 97117123; Zayavl. 30.09.97; Opubl. 10.07.2002. Byul. 19 - 494 p.
6. Kulikov VY. U., Ruyatkina L. A., Sorokin M. Y. U., SHabanova E. S. i dr. Ocenka legkih uglevodorodov v vydyhaemom vozduhe u studentov universiteta kak prediktora metabolicheskih narushenij // Journal of Siberian Medical Sciences.2010.- No. 3. [in Russian].
7. Kulikov VY. U. i dr. Soderzhanie acetona v vydyhaemom vozduhe i osobennosti metabolicheskih narushenij u bol'nyh saharnym diabetom // Setevoe nauchnoe izdanie "Medicina i obrazovanie v Sibiri".2010.-No. 6 [in Russian].
8. Biomarkery i ocenka riska. koncepcii i principy.- Z. Heneva: Vsemirnaya organizaciya zdravoohraneniya, 1996. [in Russian].
9. Stepanov E. V. Metody vysokochuvstvitel'nogo gazovogo analiza molekul-biomarkerov v issledovaniyah vydyhaemogo vozduha // Trudy instituta obshchej fiziki im. A. M. Prohorova.2005.- T. 61.- P. 5-47. [in Russian].
10. Martin A. N., Farquar G. R., Jones A. D., Frank M. Human breath analysis: methods for sample collection and reduction of localized background effects // Analytical and Bioanalytical Chemistry.2010.-Vol. 396.- No. 2.- P. 739-750.
11. Plavnik R. G., Nevmerzhickij V. I., Butorova L. I., Plavnik T. E. Sravnitel'naya ocenka mass-spektrometrii i infrakrasnoj spektrometrii pri provedenii 13S-ureaznogo dyhatel'nogo testa na Helicobacter pylori // Klinicheskaya medicina.2015.- T. 93(9).-T. 42-45. [in Russian].
12. Sidorenko G. I., Kolyadko M. G., Zolotuhina S. F. Neinvazivnye metody diagnostiki po kondensatu vydy-haemogo vozduha i ih znachenie na primere opredeleniya holesterina // Mezhdunarodnyj medicinskij zhurnal.2009.-No. 1.- P. 31-35. [in Russian].
13. YAshin A. Opredelenie biomarkerov metodom HPLC s amperometricheskim detektirovaniem // Anali-tika.2016.-4(29).- P. 106-112. [in Russian].
14. Malysheva A. O., Baldin M. N., Gruznov V. M., Blinova L. V. Vnelaboratornyj ekspressnyj gazohromatogra-ficheskij sposob analiza vydyhaemogo chelovekom vozduha s avtomatizirovannoj graduirovkoj // Analitika i kontrol'.2018.- T. 22. - No. 2.- P. 177-185. Doi: 10.15826/analitika. 2018.22.2.007 [in Russian].
15. Bukreeva E. B., Bulanova A. A., Kistenev Y. U. V. Vozmozhnosti primeneniya gazoanaliza vydyhaemogo vozduha pri bronholegochnyh zabolevaniyah // Byulleten' sibirskoj mediciny.2014.- T. 13. - No. 5.-P. 122-129. [in Russian].
16. Gudilin E. A., Semenova A. A., Eremina E. O., Brazhe N. A., Gudilina E. A., Danzanova T. Y. U., Maksi-mov G. V., Veselova I. A. Perspektivnye metody neinvazivnoj medicinskoj diagnostiki s ispol'zovaniem nanomaterialov: spektroskopiya gigantskogo kombinacionnogo rasseyaniya v issledovanii kle-tok, kletochnyh organell, markerov nejromediatornogo obmena // Vestnik RGMU.2018 .- No. 6.-P. 62-73. [in Russian].
17. Navas M. J., Jimenez A. M., Asuero A. G. Human biomarkers in breath by photoacoustic spectroscopy // Clinica Chimica Acta.2012. - Vol. 413.- P. 1171-1178.
18. Arslanov D. D., Spunei M., Mandon J. et al. Continuous-wave optical parametric oscillator based infrared spectroscopy for sensitive molecular gas sensing // Laser & Photonics Reviews.2013.- Vol. 7.- No. 2.-P. 188-206.
19. Stepanov E. V., Kasoev S. G. Mnogokomponentnyj analiz biomarkerov v vydyhaemom vozduhe metodami diodnoj lazernoj spektroskopii // Optika i spektroskopiya 2019. - T. 126. - Vyp. 6.- P. 810-819. [ in Russian].
20. Kornienko E. A., Milejko V. E., Samokish V. A. i dr. Neinvazivnye metody diagnostiki infekcii, vyzvannoj Helicobacterpylori // Pediatriya, 1999. - No. 1. - P. 37-41. [in Russian].
21. Grishina M. E., Bazhenova I. I., Volodina O. A., Kornopeleva L. S., Pashkova N. V., Pinyaeva E. G., CHer-nova A. A. Novyj metod vyyavleniya helikobaktera pilori u detej // Rossijskij pediatricheskij zhurnal, 1998.- No. 5.- P. 65-67. [in Russian].
22. Kuznecov V. I., Tarakanov S. A., Ryzhakov N. I., Kogan V. T., Kozlenok A. V., Rassadina A. A. Metod vysokochuvstvitel'noj neinvazivnoj diagnostiki funkcional'nogo sostoyaniya organizma // Vestnik novyh medicinskih tekhnologij, 2013. - No. 1. [in Russian].
23. Ilyasov L. V., Ivanova N. I. Izmeritel'naya ustanovka s differencial'nym generatornym fotoionizacionnym detektorom dlya opredeleniya biomarkerov v vydyhaemom gaze // Biotekhnosfera.2016.- No. 1(43).-P. 17-20. [in Russian].
24. Kopylov F. Y. U. Perspektivy diagnostiki razlichnyh zabolevanij po sostavu vydyhaemogo vozduha // Klinicheskaya medicina.2013.-No. 10.-P. 16-21. [ in Russian].
25. Vaks V. L., Domracheva E. G., Sobakinskaya E. A., CHernyaeva M. B. Analiz vydyhaemogo vozduha: fizicheskie metody, pribory i medicinskaya diagnostika // Uspekhi fizicheskih nauk.2014.- T. 184.-No. 7.- P. 739-758. [in Russian].
26. Lukash S. L. Problemy diagnostiki nekotoryh zabolevanij po vydyhaemomu vozduhu // Komp'yuterni zasobi, merezhi ta sistemi. 2010.- No. 9.- P. 62-70. [in Russian].
