Exhaled breath analysis: the new frontier in medical testing
With each breath we exhale, thousands of molecules are expelled in our breath and each one of us has a 'breathprint' that can tell a lot about his or her state of health. While this may be news to some, it should not be to people in medicine. For one can argue that the field of breath anal...
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description | With each breath we exhale, thousands of molecules are expelled in our breath and each one of us has a 'breathprint' that can tell a lot about his or her state of health. While this may be news to some, it should not be to people in medicine. For one can argue that the field of breath analysis is as old as the field of medicine itself. Hippocrates described fetor oris and fetor hepaticus in his treatise on breath aroma and disease, Lavoisier and Laplace in 1784 showed that respiration consumes oxygen and eliminates carbon dioxide [1], Nebelthau in the mid 1800s showed that diabetics emit breath acetone [2], and Anstie in 1874 isolated ethanol from breath (which is the basis of breath alcohol testing today) [3].The end of the 20th century and the beginning of the 21st century, however, have arguably witnessed a revolution in our understanding of the constituents of exhaled breath and the development of the field of breath analysis and testing. A major breakthrough in the scientific study of breath started in the 1970s when Linus Pauling demonstrated that there is more to exhaled breath than the classic gases of nitrogen, oxygen, carbon dioxide and water vapor, a lot more. Based on gas–liquid partition chromatography analysis, Linus Pauling reported the presence of 250 substances in exhaled breath [4]. With modern mass spectrometry (MS) and gas chromatography mass spectrometry (GC-MS) instruments, we can now identify more than 1000 unique substances in exhaled breath. These substances include elemental gases like nitric oxide and carbon monoxide and a multitude of volatile organic compounds. Exhaled breath also carries aerosolized droplets collected as 'exhaled breath condensate' that have non-volatile compounds like proteins dissolved in them as well.We now have the technology to test for any and all of these components. Thanks to major breakthroughs in new technologies (infrared, electrochemical, chemiluminescence, and others) and the availability of very sensitive mass spectrometers, the field of breath analysis has made considerable advances in the 21st century. Several methods are now in clinical use or about ready to enter that arena. There are currently commercially available analyzers that can measure NO levels in exhaled breath to the parts per billion (ppb) range and carbon monoxide to the parts per million (ppm) range [5]. Sensitive mass spectrometers can measure volatile compounds on breath down to the parts per trillion (ppt) range. Aerosolized |
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While this may be news to some, it should not be to people in medicine. For one can argue that the field of breath analysis is as old as the field of medicine itself. Hippocrates described fetor oris and fetor hepaticus in his treatise on breath aroma and disease, Lavoisier and Laplace in 1784 showed that respiration consumes oxygen and eliminates carbon dioxide [1], Nebelthau in the mid 1800s showed that diabetics emit breath acetone [2], and Anstie in 1874 isolated ethanol from breath (which is the basis of breath alcohol testing today) [3].The end of the 20th century and the beginning of the 21st century, however, have arguably witnessed a revolution in our understanding of the constituents of exhaled breath and the development of the field of breath analysis and testing. A major breakthrough in the scientific study of breath started in the 1970s when Linus Pauling demonstrated that there is more to exhaled breath than the classic gases of nitrogen, oxygen, carbon dioxide and water vapor, a lot more. Based on gas–liquid partition chromatography analysis, Linus Pauling reported the presence of 250 substances in exhaled breath [4]. With modern mass spectrometry (MS) and gas chromatography mass spectrometry (GC-MS) instruments, we can now identify more than 1000 unique substances in exhaled breath. These substances include elemental gases like nitric oxide and carbon monoxide and a multitude of volatile organic compounds. Exhaled breath also carries aerosolized droplets collected as 'exhaled breath condensate' that have non-volatile compounds like proteins dissolved in them as well.We now have the technology to test for any and all of these components. Thanks to major breakthroughs in new technologies (infrared, electrochemical, chemiluminescence, and others) and the availability of very sensitive mass spectrometers, the field of breath analysis has made considerable advances in the 21st century. Several methods are now in clinical use or about ready to enter that arena. There are currently commercially available analyzers that can measure NO levels in exhaled breath to the parts per billion (ppb) range and carbon monoxide to the parts per million (ppm) range [5]. Sensitive mass spectrometers can measure volatile compounds on breath down to the parts per trillion (ppt) range. Aerosolized droplets in exhaled breath can be captured by a variety of methods and analyzed for a wide range of biomarkers from metabolic end products to proteins to a variety of cytokines and chemokines, and the possibilities continue to expand [6]. A major hurdle that faced this field as it transitions from the laboratory to clinical testing has been the standardization of sample collection methods. To advance in this area, there had to be a close collaboration between technical experts who typically have a device looking for clinical indication, the medical experts who have the clinical problem looking for a test/biomarker that can be helpful in diagnosis or monitoring, and industry/commercial experts who can build and commercialize the final product. One great example of how the collaboration between technical, medical, and commercial professionals has resulted in a clinically useful tool is the measurement of exhaled nitric oxide (NO) in exhaled breath for monitoring airway inflammation. The advent of chemiluminescence analyzers in the early 1990s allowed the detection of low (ppb) levels of NO in exhaled breath [7]. This was quickly followed by the observation that patients with asthma had higher than normal levels of NO in their exhaled breath that was later linked to eosinophilic airway inflammation [8, 9]. Standardization of the gas collection methods and measurement techniques allowed the industry to build the next generation of analyzers suitable for use in the clinical setting [10, 11]. In 2003 the FDA approved the first desktop NO analyzer for monitoring airway inflammation in asthma [5]. The use of exhaled NO in monitoring asthma is useful for several reasons. It is non-invasive, it can be performed repeatedly, and it can be used in children and patients with severe airflow obstruction where other techniques are difficult or not possible to perform. Exhaled NO may also be more sensitive than currently available tests in detecting airway inflammation, which may allow more optimum therapy [12–19]. As breath analysis offers a window on lung physiology and disease, exhaled breath testing is becoming an increasingly important non-invasive diagnostic method that can be used in the evaluation of health and disease states in the lung and beyond. A few years ago the new International Association of Breath Research (IABR) was established to have a platform for researchers in the field. The association holds an annual meeting and the newly established Journal of Breath Research (JBR) is the official publication of the IABR. In November 2007, the First Breath Analysis Summit/3rd annual meeting of IABR was held on the Cleveland Clinic Campus in Cleveland, Ohio, USA. The Summit brought together industry executives and entrepreneurs with scientists and clinicians to discuss key trends, future directions, and upcoming technologies in breath analysis and medicine. The major focus of the Summit was on medical applications. Topics included exhaled nitric oxide, exhaled breath condensate, electronic nose and sensor arrays, mass spectrometry and bench-top instrumentation, and cutting edge sensor technologies. Medical applications that were covered included asthma, COPD, pulmonary hypertension, other respiratory diseases, gastrointestinal diseases, occupational diseases, critical illness, and cancer. This special issue of JBR contains peer-reviewed, full articles of work presented at the Summit and represents the proceedings of this Summit.References[1] Duveen D I and Klickstein H S 1955 Antoine Laurent Lavoisier's contributions to medicine and public health Bull. Hist. Med. 29 164–79[2] Hubbard R S 1920 Determination of acetone in expired air J. Biol. Chem. 43 57–65[3] Baldwin A D 1977 Anstie's alcohol limit: Francis Edmund Anstie 1833–1874 Am. J. Public Health 67 679–81[4] Pauling L, Robinson A B, Teranishi R and Cary P 1971 Quantitative analysis of urine vapor and breath by gas–liquid partition chromatography Proc. Natl Acad. Sci. USA 68 2374–6[5] Gill M, Graff G R, Adler A J and Dweik R A 2006 Validation study of fractional exhaled nitric oxide measurements using a handheld monitoring device J. Asthma 43 731–4[6] Horvath I et al 2005 Exhaled breath condensate: methodological recommendations and unresolved questions Eur. Respir. J. 26 523–48[7] Gustafsson L E, Leone A M, Persson M G, Wiklund N P and Moncada S 1991 Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans Biochem. Biophys. Res. Commun. 181 852–7[8] Kharitonov S A, Yates D, Robbins R A, Logan-Sinclair R, Shinebourne E A and Barnes P J 1994 Increased nitric oxide in exhaled air of asthmatic patients Lancet 343 133–5[9] Persson M G, Zetterstrom O, Agrenius V, Ihre E and Gustafsson L E 1994 Single-breath nitric oxide measurements in asthmatic patients and smokers Lancet 343 146–7[10] American Thoracic Society 1999 Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children—1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999 Am. J. Respir. Crit. Care Med. 160 2104–17[11] American Thoracic Society 2005 ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005 Am. J. Respir. Crit. Care Med. 171 912–30[12] Dweik R A 2001 The promise and reality of nitric oxide in the diagnosis and treatment of lung disease Cleve. Clin. J. Med. 68 486, 488, 490, 493[13] Dweik R A, Comhair S A, Gaston B, Thunnissen F B, Farver C, Thomassen M J, Kavuru M, Hammel J, Abu-Soud H M and Erzurum S C 2001 NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response Proc. Natl Acad. Sci. USA 98 2622–7[14] Guo F H, Comhair S A, Zheng S, Dweik R A, Eissa N T, Thomassen M J, Calhoun W and Erzurum S C 2000 Molecular mechanisms of increased nitric oxide (NO) in asthma: evidence for transcriptional and post-translational regulation of NO synthesis J. Immunol. 164 5970–80[15] Khatri S B, Ozkan M, McCarthy K, Laskowski D, Hammel J, Dweik R A and Erzurum S C 2001 Alterations in exhaled gas profile during allergen-induced asthmatic response Am. J. Respir. Crit. Care Med. 164 1844–8[16] Khatri S B, Hammel J, Kavuru M S, Erzurum S C and Dweik R A 2003 Temporal association of nitric oxide levels and airflow in asthma after whole lung allergen challenge J. Appl. Physiol. 95 436-40; discussion 435[17] Dweik R A 2002 Nitric oxide reactions in the asthmatic airway Disease Markers in Exhaled Breath: basic mechanisms and clinical applications (NATO Science Series) ed N Marczin and M H Yacoub (Amsterdam: IOS Press) pp 159–66[18] Grob N M and Dweik R A 2008 Exhaled nitric oxide in asthma. From diagnosis, to monitoring, to screening: are we there yet? Chest 133 837–9[19] Ozkan M and Dweik R A 2001 Nitric oxide and airway reactivity Clin. Pulmonary Med. 8 199–206</description><identifier>ISSN: 1752-7163</identifier><identifier>ISSN: 1752-7155</identifier><identifier>EISSN: 1752-7163</identifier><identifier>DOI: 10.1088/1752-7163/2/3/030301</identifier><identifier>PMID: 25243021</identifier><language>eng</language><publisher>England: IOP Publishing</publisher><subject>21st century ; Allergens ; Asthma ; Biomarkers ; Carbon monoxide ; Chromatography ; Collaboration ; Disease ; Gases ; Inflammation ; Mass spectrometry ; Measurement techniques ; Medicine ; Nitric oxide ; Pauling, Linus Carl ; Public health ; Scientific imaging ; VOCs ; Volatile organic compounds</subject><ispartof>Journal of breath research, 2008-09, Vol.2 (3), p.030301</ispartof><rights>Copyright IOP Publishing Sep 2008</rights><rights>2008 IOP Publishing Ltd 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c578t-e2d9f8384bdee0a94399661845d022a72afa2d94f6e36ea6fd1c66fb7ff78c173</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://iopscience.iop.org/article/10.1088/1752-7163/2/3/030301/pdf$$EPDF$$P50$$Giop$$H</linktopdf><link.rule.ids>230,314,780,784,885,27924,27925,53830,53910</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25243021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dweik, Raed A</creatorcontrib><creatorcontrib>Amann, Anton</creatorcontrib><title>Exhaled breath analysis: the new frontier in medical testing</title><title>Journal of breath research</title><addtitle>J Breath Res</addtitle><description>With each breath we exhale, thousands of molecules are expelled in our breath and each one of us has a 'breathprint' that can tell a lot about his or her state of health. While this may be news to some, it should not be to people in medicine. For one can argue that the field of breath analysis is as old as the field of medicine itself. Hippocrates described fetor oris and fetor hepaticus in his treatise on breath aroma and disease, Lavoisier and Laplace in 1784 showed that respiration consumes oxygen and eliminates carbon dioxide [1], Nebelthau in the mid 1800s showed that diabetics emit breath acetone [2], and Anstie in 1874 isolated ethanol from breath (which is the basis of breath alcohol testing today) [3].The end of the 20th century and the beginning of the 21st century, however, have arguably witnessed a revolution in our understanding of the constituents of exhaled breath and the development of the field of breath analysis and testing. A major breakthrough in the scientific study of breath started in the 1970s when Linus Pauling demonstrated that there is more to exhaled breath than the classic gases of nitrogen, oxygen, carbon dioxide and water vapor, a lot more. Based on gas–liquid partition chromatography analysis, Linus Pauling reported the presence of 250 substances in exhaled breath [4]. With modern mass spectrometry (MS) and gas chromatography mass spectrometry (GC-MS) instruments, we can now identify more than 1000 unique substances in exhaled breath. These substances include elemental gases like nitric oxide and carbon monoxide and a multitude of volatile organic compounds. Exhaled breath also carries aerosolized droplets collected as 'exhaled breath condensate' that have non-volatile compounds like proteins dissolved in them as well.We now have the technology to test for any and all of these components. Thanks to major breakthroughs in new technologies (infrared, electrochemical, chemiluminescence, and others) and the availability of very sensitive mass spectrometers, the field of breath analysis has made considerable advances in the 21st century. Several methods are now in clinical use or about ready to enter that arena. There are currently commercially available analyzers that can measure NO levels in exhaled breath to the parts per billion (ppb) range and carbon monoxide to the parts per million (ppm) range [5]. Sensitive mass spectrometers can measure volatile compounds on breath down to the parts per trillion (ppt) range. Aerosolized droplets in exhaled breath can be captured by a variety of methods and analyzed for a wide range of biomarkers from metabolic end products to proteins to a variety of cytokines and chemokines, and the possibilities continue to expand [6]. A major hurdle that faced this field as it transitions from the laboratory to clinical testing has been the standardization of sample collection methods. To advance in this area, there had to be a close collaboration between technical experts who typically have a device looking for clinical indication, the medical experts who have the clinical problem looking for a test/biomarker that can be helpful in diagnosis or monitoring, and industry/commercial experts who can build and commercialize the final product. One great example of how the collaboration between technical, medical, and commercial professionals has resulted in a clinically useful tool is the measurement of exhaled nitric oxide (NO) in exhaled breath for monitoring airway inflammation. The advent of chemiluminescence analyzers in the early 1990s allowed the detection of low (ppb) levels of NO in exhaled breath [7]. This was quickly followed by the observation that patients with asthma had higher than normal levels of NO in their exhaled breath that was later linked to eosinophilic airway inflammation [8, 9]. Standardization of the gas collection methods and measurement techniques allowed the industry to build the next generation of analyzers suitable for use in the clinical setting [10, 11]. In 2003 the FDA approved the first desktop NO analyzer for monitoring airway inflammation in asthma [5]. The use of exhaled NO in monitoring asthma is useful for several reasons. It is non-invasive, it can be performed repeatedly, and it can be used in children and patients with severe airflow obstruction where other techniques are difficult or not possible to perform. Exhaled NO may also be more sensitive than currently available tests in detecting airway inflammation, which may allow more optimum therapy [12–19]. As breath analysis offers a window on lung physiology and disease, exhaled breath testing is becoming an increasingly important non-invasive diagnostic method that can be used in the evaluation of health and disease states in the lung and beyond. A few years ago the new International Association of Breath Research (IABR) was established to have a platform for researchers in the field. The association holds an annual meeting and the newly established Journal of Breath Research (JBR) is the official publication of the IABR. In November 2007, the First Breath Analysis Summit/3rd annual meeting of IABR was held on the Cleveland Clinic Campus in Cleveland, Ohio, USA. The Summit brought together industry executives and entrepreneurs with scientists and clinicians to discuss key trends, future directions, and upcoming technologies in breath analysis and medicine. The major focus of the Summit was on medical applications. Topics included exhaled nitric oxide, exhaled breath condensate, electronic nose and sensor arrays, mass spectrometry and bench-top instrumentation, and cutting edge sensor technologies. Medical applications that were covered included asthma, COPD, pulmonary hypertension, other respiratory diseases, gastrointestinal diseases, occupational diseases, critical illness, and cancer. This special issue of JBR contains peer-reviewed, full articles of work presented at the Summit and represents the proceedings of this Summit.References[1] Duveen D I and Klickstein H S 1955 Antoine Laurent Lavoisier's contributions to medicine and public health Bull. Hist. Med. 29 164–79[2] Hubbard R S 1920 Determination of acetone in expired air J. Biol. Chem. 43 57–65[3] Baldwin A D 1977 Anstie's alcohol limit: Francis Edmund Anstie 1833–1874 Am. J. Public Health 67 679–81[4] Pauling L, Robinson A B, Teranishi R and Cary P 1971 Quantitative analysis of urine vapor and breath by gas–liquid partition chromatography Proc. Natl Acad. Sci. USA 68 2374–6[5] Gill M, Graff G R, Adler A J and Dweik R A 2006 Validation study of fractional exhaled nitric oxide measurements using a handheld monitoring device J. Asthma 43 731–4[6] Horvath I et al 2005 Exhaled breath condensate: methodological recommendations and unresolved questions Eur. Respir. J. 26 523–48[7] Gustafsson L E, Leone A M, Persson M G, Wiklund N P and Moncada S 1991 Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans Biochem. Biophys. Res. Commun. 181 852–7[8] Kharitonov S A, Yates D, Robbins R A, Logan-Sinclair R, Shinebourne E A and Barnes P J 1994 Increased nitric oxide in exhaled air of asthmatic patients Lancet 343 133–5[9] Persson M G, Zetterstrom O, Agrenius V, Ihre E and Gustafsson L E 1994 Single-breath nitric oxide measurements in asthmatic patients and smokers Lancet 343 146–7[10] American Thoracic Society 1999 Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children—1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999 Am. J. Respir. Crit. Care Med. 160 2104–17[11] American Thoracic Society 2005 ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005 Am. J. Respir. Crit. Care Med. 171 912–30[12] Dweik R A 2001 The promise and reality of nitric oxide in the diagnosis and treatment of lung disease Cleve. Clin. J. Med. 68 486, 488, 490, 493[13] Dweik R A, Comhair S A, Gaston B, Thunnissen F B, Farver C, Thomassen M J, Kavuru M, Hammel J, Abu-Soud H M and Erzurum S C 2001 NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response Proc. Natl Acad. Sci. USA 98 2622–7[14] Guo F H, Comhair S A, Zheng S, Dweik R A, Eissa N T, Thomassen M J, Calhoun W and Erzurum S C 2000 Molecular mechanisms of increased nitric oxide (NO) in asthma: evidence for transcriptional and post-translational regulation of NO synthesis J. Immunol. 164 5970–80[15] Khatri S B, Ozkan M, McCarthy K, Laskowski D, Hammel J, Dweik R A and Erzurum S C 2001 Alterations in exhaled gas profile during allergen-induced asthmatic response Am. J. Respir. Crit. Care Med. 164 1844–8[16] Khatri S B, Hammel J, Kavuru M S, Erzurum S C and Dweik R A 2003 Temporal association of nitric oxide levels and airflow in asthma after whole lung allergen challenge J. Appl. Physiol. 95 436-40; discussion 435[17] Dweik R A 2002 Nitric oxide reactions in the asthmatic airway Disease Markers in Exhaled Breath: basic mechanisms and clinical applications (NATO Science Series) ed N Marczin and M H Yacoub (Amsterdam: IOS Press) pp 159–66[18] Grob N M and Dweik R A 2008 Exhaled nitric oxide in asthma. From diagnosis, to monitoring, to screening: are we there yet? Chest 133 837–9[19] Ozkan M and Dweik R A 2001 Nitric oxide and airway reactivity Clin. Pulmonary Med. 8 199–206</description><subject>21st century</subject><subject>Allergens</subject><subject>Asthma</subject><subject>Biomarkers</subject><subject>Carbon monoxide</subject><subject>Chromatography</subject><subject>Collaboration</subject><subject>Disease</subject><subject>Gases</subject><subject>Inflammation</subject><subject>Mass spectrometry</subject><subject>Measurement techniques</subject><subject>Medicine</subject><subject>Nitric oxide</subject><subject>Pauling, Linus Carl</subject><subject>Public health</subject><subject>Scientific imaging</subject><subject>VOCs</subject><subject>Volatile organic compounds</subject><issn>1752-7163</issn><issn>1752-7155</issn><issn>1752-7163</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqNkV1LwzAYhYMobn78A5GCN4LM5qtJKiLImB8geKPXIWvfbBldO5NO3b83ozpUvJBcJCTPezg5B6Ejgs8JViolMqMDSQRLacpSzOIiW6i_ud7-du6hvRBmGAuOVb6LejSjnGFK-uhy9D41FZTJ2INpp4mpTbUKLlwk7RSSGt4S65u6deATVydzKF1hqqSF0Lp6coB2rKkCHH7u--j5ZvQ0vBs8PN7eD68fBkUmVTsAWuZWMcXHJQA2OWd5LgRRPCsxpUZSY01EuBXABBhhS1IIYcfSWqkKItk-uup0F8txtFBA3XpT6YV3c-NXujFO_3yp3VRPmlfNiZCKiShw-ingm5dlNK_nLhRQVaaGZhk0USzLckUkj-jJL3TWLH1MJWgqGcNCEZFHindU4ZsQPNiNGYL1uh69zl6vs9dUM93VE8eOv39kM_TVRwTSDnDN4r-SZ39M_EHqRWnZB6JVpeM</recordid><startdate>20080901</startdate><enddate>20080901</enddate><creator>Dweik, Raed A</creator><creator>Amann, Anton</creator><general>IOP Publishing</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080901</creationdate><title>Exhaled breath analysis: the new frontier in medical testing</title><author>Dweik, Raed A ; Amann, Anton</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c578t-e2d9f8384bdee0a94399661845d022a72afa2d94f6e36ea6fd1c66fb7ff78c173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>21st century</topic><topic>Allergens</topic><topic>Asthma</topic><topic>Biomarkers</topic><topic>Carbon monoxide</topic><topic>Chromatography</topic><topic>Collaboration</topic><topic>Disease</topic><topic>Gases</topic><topic>Inflammation</topic><topic>Mass spectrometry</topic><topic>Measurement techniques</topic><topic>Medicine</topic><topic>Nitric oxide</topic><topic>Pauling, Linus Carl</topic><topic>Public health</topic><topic>Scientific imaging</topic><topic>VOCs</topic><topic>Volatile organic compounds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dweik, Raed A</creatorcontrib><creatorcontrib>Amann, Anton</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of breath research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dweik, Raed A</au><au>Amann, Anton</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exhaled breath analysis: the new frontier in medical testing</atitle><jtitle>Journal of breath research</jtitle><addtitle>J Breath Res</addtitle><date>2008-09-01</date><risdate>2008</risdate><volume>2</volume><issue>3</issue><spage>030301</spage><pages>030301-</pages><issn>1752-7163</issn><issn>1752-7155</issn><eissn>1752-7163</eissn><abstract>With each breath we exhale, thousands of molecules are expelled in our breath and each one of us has a 'breathprint' that can tell a lot about his or her state of health. While this may be news to some, it should not be to people in medicine. For one can argue that the field of breath analysis is as old as the field of medicine itself. Hippocrates described fetor oris and fetor hepaticus in his treatise on breath aroma and disease, Lavoisier and Laplace in 1784 showed that respiration consumes oxygen and eliminates carbon dioxide [1], Nebelthau in the mid 1800s showed that diabetics emit breath acetone [2], and Anstie in 1874 isolated ethanol from breath (which is the basis of breath alcohol testing today) [3].The end of the 20th century and the beginning of the 21st century, however, have arguably witnessed a revolution in our understanding of the constituents of exhaled breath and the development of the field of breath analysis and testing. A major breakthrough in the scientific study of breath started in the 1970s when Linus Pauling demonstrated that there is more to exhaled breath than the classic gases of nitrogen, oxygen, carbon dioxide and water vapor, a lot more. Based on gas–liquid partition chromatography analysis, Linus Pauling reported the presence of 250 substances in exhaled breath [4]. With modern mass spectrometry (MS) and gas chromatography mass spectrometry (GC-MS) instruments, we can now identify more than 1000 unique substances in exhaled breath. These substances include elemental gases like nitric oxide and carbon monoxide and a multitude of volatile organic compounds. Exhaled breath also carries aerosolized droplets collected as 'exhaled breath condensate' that have non-volatile compounds like proteins dissolved in them as well.We now have the technology to test for any and all of these components. Thanks to major breakthroughs in new technologies (infrared, electrochemical, chemiluminescence, and others) and the availability of very sensitive mass spectrometers, the field of breath analysis has made considerable advances in the 21st century. Several methods are now in clinical use or about ready to enter that arena. There are currently commercially available analyzers that can measure NO levels in exhaled breath to the parts per billion (ppb) range and carbon monoxide to the parts per million (ppm) range [5]. Sensitive mass spectrometers can measure volatile compounds on breath down to the parts per trillion (ppt) range. Aerosolized droplets in exhaled breath can be captured by a variety of methods and analyzed for a wide range of biomarkers from metabolic end products to proteins to a variety of cytokines and chemokines, and the possibilities continue to expand [6]. A major hurdle that faced this field as it transitions from the laboratory to clinical testing has been the standardization of sample collection methods. To advance in this area, there had to be a close collaboration between technical experts who typically have a device looking for clinical indication, the medical experts who have the clinical problem looking for a test/biomarker that can be helpful in diagnosis or monitoring, and industry/commercial experts who can build and commercialize the final product. One great example of how the collaboration between technical, medical, and commercial professionals has resulted in a clinically useful tool is the measurement of exhaled nitric oxide (NO) in exhaled breath for monitoring airway inflammation. The advent of chemiluminescence analyzers in the early 1990s allowed the detection of low (ppb) levels of NO in exhaled breath [7]. This was quickly followed by the observation that patients with asthma had higher than normal levels of NO in their exhaled breath that was later linked to eosinophilic airway inflammation [8, 9]. Standardization of the gas collection methods and measurement techniques allowed the industry to build the next generation of analyzers suitable for use in the clinical setting [10, 11]. In 2003 the FDA approved the first desktop NO analyzer for monitoring airway inflammation in asthma [5]. The use of exhaled NO in monitoring asthma is useful for several reasons. It is non-invasive, it can be performed repeatedly, and it can be used in children and patients with severe airflow obstruction where other techniques are difficult or not possible to perform. Exhaled NO may also be more sensitive than currently available tests in detecting airway inflammation, which may allow more optimum therapy [12–19]. As breath analysis offers a window on lung physiology and disease, exhaled breath testing is becoming an increasingly important non-invasive diagnostic method that can be used in the evaluation of health and disease states in the lung and beyond. A few years ago the new International Association of Breath Research (IABR) was established to have a platform for researchers in the field. The association holds an annual meeting and the newly established Journal of Breath Research (JBR) is the official publication of the IABR. In November 2007, the First Breath Analysis Summit/3rd annual meeting of IABR was held on the Cleveland Clinic Campus in Cleveland, Ohio, USA. The Summit brought together industry executives and entrepreneurs with scientists and clinicians to discuss key trends, future directions, and upcoming technologies in breath analysis and medicine. The major focus of the Summit was on medical applications. Topics included exhaled nitric oxide, exhaled breath condensate, electronic nose and sensor arrays, mass spectrometry and bench-top instrumentation, and cutting edge sensor technologies. Medical applications that were covered included asthma, COPD, pulmonary hypertension, other respiratory diseases, gastrointestinal diseases, occupational diseases, critical illness, and cancer. This special issue of JBR contains peer-reviewed, full articles of work presented at the Summit and represents the proceedings of this Summit.References[1] Duveen D I and Klickstein H S 1955 Antoine Laurent Lavoisier's contributions to medicine and public health Bull. Hist. Med. 29 164–79[2] Hubbard R S 1920 Determination of acetone in expired air J. Biol. Chem. 43 57–65[3] Baldwin A D 1977 Anstie's alcohol limit: Francis Edmund Anstie 1833–1874 Am. J. Public Health 67 679–81[4] Pauling L, Robinson A B, Teranishi R and Cary P 1971 Quantitative analysis of urine vapor and breath by gas–liquid partition chromatography Proc. Natl Acad. Sci. USA 68 2374–6[5] Gill M, Graff G R, Adler A J and Dweik R A 2006 Validation study of fractional exhaled nitric oxide measurements using a handheld monitoring device J. Asthma 43 731–4[6] Horvath I et al 2005 Exhaled breath condensate: methodological recommendations and unresolved questions Eur. Respir. J. 26 523–48[7] Gustafsson L E, Leone A M, Persson M G, Wiklund N P and Moncada S 1991 Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans Biochem. Biophys. Res. Commun. 181 852–7[8] Kharitonov S A, Yates D, Robbins R A, Logan-Sinclair R, Shinebourne E A and Barnes P J 1994 Increased nitric oxide in exhaled air of asthmatic patients Lancet 343 133–5[9] Persson M G, Zetterstrom O, Agrenius V, Ihre E and Gustafsson L E 1994 Single-breath nitric oxide measurements in asthmatic patients and smokers Lancet 343 146–7[10] American Thoracic Society 1999 Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children—1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999 Am. J. Respir. Crit. Care Med. 160 2104–17[11] American Thoracic Society 2005 ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005 Am. J. Respir. Crit. Care Med. 171 912–30[12] Dweik R A 2001 The promise and reality of nitric oxide in the diagnosis and treatment of lung disease Cleve. Clin. J. Med. 68 486, 488, 490, 493[13] Dweik R A, Comhair S A, Gaston B, Thunnissen F B, Farver C, Thomassen M J, Kavuru M, Hammel J, Abu-Soud H M and Erzurum S C 2001 NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response Proc. Natl Acad. Sci. USA 98 2622–7[14] Guo F H, Comhair S A, Zheng S, Dweik R A, Eissa N T, Thomassen M J, Calhoun W and Erzurum S C 2000 Molecular mechanisms of increased nitric oxide (NO) in asthma: evidence for transcriptional and post-translational regulation of NO synthesis J. Immunol. 164 5970–80[15] Khatri S B, Ozkan M, McCarthy K, Laskowski D, Hammel J, Dweik R A and Erzurum S C 2001 Alterations in exhaled gas profile during allergen-induced asthmatic response Am. J. Respir. Crit. Care Med. 164 1844–8[16] Khatri S B, Hammel J, Kavuru M S, Erzurum S C and Dweik R A 2003 Temporal association of nitric oxide levels and airflow in asthma after whole lung allergen challenge J. Appl. Physiol. 95 436-40; discussion 435[17] Dweik R A 2002 Nitric oxide reactions in the asthmatic airway Disease Markers in Exhaled Breath: basic mechanisms and clinical applications (NATO Science Series) ed N Marczin and M H Yacoub (Amsterdam: IOS Press) pp 159–66[18] Grob N M and Dweik R A 2008 Exhaled nitric oxide in asthma. From diagnosis, to monitoring, to screening: are we there yet? Chest 133 837–9[19] Ozkan M and Dweik R A 2001 Nitric oxide and airway reactivity Clin. Pulmonary Med. 8 199–206</abstract><cop>England</cop><pub>IOP Publishing</pub><pmid>25243021</pmid><doi>10.1088/1752-7163/2/3/030301</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1752-7163 |
ispartof | Journal of breath research, 2008-09, Vol.2 (3), p.030301 |
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source | Institute of Physics Journals |
subjects | 21st century Allergens Asthma Biomarkers Carbon monoxide Chromatography Collaboration Disease Gases Inflammation Mass spectrometry Measurement techniques Medicine Nitric oxide Pauling, Linus Carl Public health Scientific imaging VOCs Volatile organic compounds |
title | Exhaled breath analysis: the new frontier in medical testing |
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