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Article ; Online: Breath Metabolites to Diagnose Infection.

Berna, Amalia Z / Odom John, Audrey R

2021 Volume 68, Issue 1, Page(s) 43–51

Abstract: Background: Starkly highlighted by the current COVID-19 pandemic, infectious diseases continue to have an outsized impact on human health worldwide. Diagnostic testing for infection can be challenging due to resource limitations, time constraints, or ... ...

Abstract	Background: Starkly highlighted by the current COVID-19 pandemic, infectious diseases continue to have an outsized impact on human health worldwide. Diagnostic testing for infection can be challenging due to resource limitations, time constraints, or shortcomings in the accuracy of existing diagnostics. Rapid, simple diagnostics are highly desirable. There is increasing interest in the development of diagnostics that use exhaled breath analysis as a convenient and safe diagnostic method, as breath sampling is noninvasive, secure, and easy to perform. Volatile organic compounds (VOCs) present in exhaled breath reflect the fingerprint of the underlying metabolic and biophysical processes during disease. Content: In this review, we overview the major biomarkers present in exhaled breath in infectious diseases. We outline the promising recent advances in breath-based diagnosis of respiratory infections, including those caused by influenza virus, SARS-CoV-2, Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Aspergillus fumigatus. In addition, we review the current landscape of diagnosis of 2 other globally important infections: Helicobacter pylori gastrointestinal infection and malaria. Summary: Characteristic and reproducible breath VOCs are associated with several infectious diseases, suggesting breath analysis as a promising strategy for diagnostic development. Ongoing challenges include poor standardization of breath collection and analysis and lack of validation studies. Further research is required to expand the applicability of breath analysis to clinical settings.
MeSH term(s)	Breath Tests ; Communicable Diseases/diagnosis ; Exhalation ; Humans ; Volatile Organic Compounds/analysis
Chemical Substances	Volatile Organic Compounds
Language	English
Publishing date	2021-12-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1093/clinchem/hvab218
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Article ; Online: Volatile profiling distinguishes

Berna, Amalia Z / Merriman, Joseph A / Mellett, Leah / Parchment, Danealle K / Caparon, Michael G / Odom John, Audrey R

mSphere

2023 Volume 8, Issue 5, Page(s) e0019423

Abstract: Sore throat is one of the most common complaints encountered in the ambulatory clinical setting. Rapid, culture-independent diagnostic techniques that do not rely on pharyngeal swabs would be highly valuable as a point-of-care strategy to guide ... ...

Abstract	Sore throat is one of the most common complaints encountered in the ambulatory clinical setting. Rapid, culture-independent diagnostic techniques that do not rely on pharyngeal swabs would be highly valuable as a point-of-care strategy to guide outpatient antibiotic treatment. Despite the promise of this approach, efforts to detect volatiles during oropharyngeal infection have yet been limited. In our research study, we sought to evaluate for specific bacterial volatile organic compounds (VOC) biomarkers in isolated cultures
MeSH term(s)	Humans ; Child ; Streptococcus pyogenes ; Streptococcal Infections/diagnosis ; Streptococcal Infections/microbiology ; Pharyngitis/diagnosis ; Pharyngitis/microbiology ; Anti-Bacterial Agents/therapeutic use ; Biomarkers
Chemical Substances	Anti-Bacterial Agents ; Biomarkers
Language	English
Publishing date	2023-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/msphere.00194-23
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation.

Vella, Laura A / Berna, Amalia Z / Blatz, Allison M / Logan, Joey / Sharma, Priya / Liu, Yang / Tedesco, Jonathan / Toland, Cara / Babiker, Leena / Hafertepe, Kathryn / Kammerman, Shane / Novacek, Josef / Akaho, Elikplim / Gonzalez, Alexander K / Taylor, Deanne / Diorio, Caroline / Balamuth, Fran / Bassiri, Hamid / Odom John, Audrey R

medRxiv : the preprint server for health sciences

2024

Abstract: Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to ... ...

Abstract	Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to misdiagnosis. To identify diagnostic discriminators at the time of emergency department presentation, we enrolled 104 children who met MIS-C screening criteria, 14 of whom were eventually diagnosed with MIS-C. Before treatment, we collected breath samples for volatiles and peripheral blood for measurement of plasma proteins and immune cell features. Clinical and laboratory features were used as inputs for a machine learning model to determine diagnostic importance. MIS-C was associated with significant changes in breath volatile organic compound (VOC) composition as well as increased plasma levels of secretory phospholipase A2 (PLA2G2A) and lipopolysaccharide binding protein (LBP). In an integrated model of all analytes, the proportion of TCRVβ21.3+ non-naive CD4 T cells expressing Ki-67 had a high sensitivity and specificity for MIS-C, with diagnostic accuracy further enhanced by low sodium and high PLA2G2A. We anticipate that accurate diagnosis will become increasingly difficult as MIS-C becomes less common. Clinical validation and application of this diagnostic model may improve outcomes in children presenting with multisystem febrile illnesses.
Language	English
Publishing date	2024-01-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.11.24301110
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Article ; Online: Stability control for breath analysis using GC-MS.

Wang, X Rosalind / Cassells, Julie / Berna, Amalia Z

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2018 Volume 1097-1098, Page(s) 27–34

Abstract: Gas chromatography mass spectrometry (GC-MS) instruments provide researchers and clinicians with a vast amount of information on sample composition, thus these instruments are seen as gold standard in breath analysis research. However, there are many ... ...

Abstract	Gas chromatography mass spectrometry (GC-MS) instruments provide researchers and clinicians with a vast amount of information on sample composition, thus these instruments are seen as gold standard in breath analysis research. However, there are many factors that can confound the data measured by GC-MS instruments. These factors will make interpretation of GC-MS data unreliable for breath analysis research. We present in this paper detailed studies of two of these factors: instrument variation over time and chemical degradation of known biomarkers during storage in sorbent tubes. We found that a single quadrupole MS showed larger variability in measurements than a quadrupole time-of-flight MS when the same mixture of chemical standards was analysed for a period of up to 8 weeks. We recommend procedures of normalising the data. Moreover, the stability studies of breath biomarkers like thioethers, previously found indicative of malaria, showed that there is a need to store the samples in sorbent tubes at low temperature, 6 °C, for no more than 20 days to avoid the total decay of the chemicals.
MeSH term(s)	Breath Tests ; Gas Chromatography-Mass Spectrometry/instrumentation ; Gas Chromatography-Mass Spectrometry/methods ; Gas Chromatography-Mass Spectrometry/standards ; Reference Standards ; Reproducibility of Results ; Volatile Organic Compounds/analysis
Chemical Substances	Volatile Organic Compounds
Language	English
Publishing date	2018-08-31
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2018.08.024
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Article: Stability control for breath analysis using GC-MS

Wang, X. Rosalind / Cassells, Julie / Berna, Amalia Z

Journal of chromatography. 2018 Oct. 15, v. 1097-1098

2018

Abstract	Gas chromatography mass spectrometry (GC-MS) instruments provide researchers and clinicians with a vast amount of information on sample composition, thus these instruments are seen as gold standard in breath analysis research. However, there are many factors that can confound the data measured by GC-MS instruments. These factors will make interpretation of GC-MS data unreliable for breath analysis research. We present in this paper detailed studies of two of these factors: instrument variation over time and chemical degradation of known biomarkers during storage in sorbent tubes. We found that a single quadrupole MS showed larger variability in measurements than a quadrupole time-of-flight MS when the same mixture of chemical standards was analysed for a period of up to 8 weeks. We recommend procedures of normalising the data. Moreover, the stability studies of breath biomarkers like thioethers, previously found indicative of malaria, showed that there is a need to store the samples in sorbent tubes at low temperature, 6 °C, for no more than 20 days to avoid the total decay of the chemicals.
Keywords	biomarkers ; chemical degradation ; gas chromatography-mass spectrometry ; malaria ; sorbents ; temperature
Language	English
Dates of publication	2018-1015
Size	p. 27-34.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	1570-0232
DOI	10.1016/j.jchromb.2018.08.024
Database	NAL-Catalogue (AGRICOLA)

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Article: Breath collection from children for disease biomarker discovery

Berna, Amalia Z / DeBosch, Brian / Stoll, Janis / Odom John, Audrey R

Journal of visualized experiments. 2019 Feb. 14, , no. 144

2019

Abstract: Breath collection and analysis can be used to discover volatile biomarkers in a number of infectious and non-infectious diseases, such as malaria, tuberculosis, lung cancer, and liver disease. This protocol describes a reproducible method for sampling ... ...

Abstract	Breath collection and analysis can be used to discover volatile biomarkers in a number of infectious and non-infectious diseases, such as malaria, tuberculosis, lung cancer, and liver disease. This protocol describes a reproducible method for sampling breath in children and then stabilizing breath samples for further analysis with gas chromatography-mass spectrometry (GC-MS). The goal of this method is to establish a standardized protocol for the acquisition of breath samples for further chemical analysis, from children aged 4-15 years. First, breath is sampled using a cardboard mouthpiece attached to a 2-way valve, which is connected to a 3 L bag. Breath analytes are then transferred to a thermal desorption tube and stored at 4-5 °C until analysis. This technique has been previously used to capture breath of children with malaria for successful breath biomarker identification. Subsequently, we have successfully applied this technique to additional pediatric cohorts. The advantage of this method is that it requires minimal cooperation on part of the patient (of particular value in pediatric populations), has a short collection period, does not require trained staff, and can be performed with portable equipment in resource-limited field settings.
Keywords	biomarkers ; breath tests ; cardboard ; chemical analysis ; chemical species ; children ; desorption ; gas chromatography-mass spectrometry ; liver diseases ; lung neoplasms ; malaria ; patients ; portable equipment ; storage temperature ; tuberculosis
Language	English
Dates of publication	2019-0214
Size	p. e59217.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/59217
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Breath Collection from Children for Disease Biomarker Discovery.

Berna, Amalia Z / DeBosch, Brian / Stoll, Janis / Odom John, Audrey R

Journal of visualized experiments : JoVE

2019 , Issue 144

Abstract	Breath collection and analysis can be used to discover volatile biomarkers in a number of infectious and non-infectious diseases, such as malaria, tuberculosis, lung cancer, and liver disease. This protocol describes a reproducible method for sampling breath in children and then stabilizing breath samples for further analysis with gas chromatography-mass spectrometry (GC-MS). The goal of this method is to establish a standardized protocol for the acquisition of breath samples for further chemical analysis, from children aged 4-15 years. First, breath is sampled using a cardboard mouthpiece attached to a 2-way valve, which is connected to a 3 L bag. Breath analytes are then transferred to a thermal desorption tube and stored at 4-5 °C until analysis. This technique has been previously used to capture breath of children with malaria for successful breath biomarker identification. Subsequently, we have successfully applied this technique to additional pediatric cohorts. The advantage of this method is that it requires minimal cooperation on part of the patient (of particular value in pediatric populations), has a short collection period, does not require trained staff, and can be performed with portable equipment in resource-limited field settings.
MeSH term(s)	Adolescent ; Biomarkers/analysis ; Breath Tests/instrumentation ; Breath Tests/methods ; Child ; Child, Preschool ; Gas Chromatography-Mass Spectrometry ; Humans ; Malaria/diagnosis ; Volatile Organic Compounds/analysis
Chemical Substances	Biomarkers ; Volatile Organic Compounds
Language	English
Publishing date	2019-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/59217
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Malaria detection using breath biomarkers.

Berna, Amalia Z / McCarthy, James S / Trowell, Stephen C

The Medical journal of Australia

2015 Volume 204, Issue 2, Page(s) 50

MeSH term(s)	Biomarkers/analysis ; Breath Tests/methods ; Humans ; Malaria/diagnosis ; Malaria, Falciparum/diagnosis ; Predictive Value of Tests ; Sensitivity and Specificity ; Sulfides/analysis
Chemical Substances	Biomarkers ; Sulfides
Language	English
Publishing date	2015-12-10
Publishing country	Australia
Document type	Journal Article
ZDB-ID	186082-3
ISSN	1326-5377 ; 0025-729X
ISSN (online)	1326-5377
ISSN	0025-729X
DOI	10.5694/mja15.01244
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Reproducible Breath Metabolite Changes in Children with SARS-CoV-2 Infection.

Berna, Amalia Z / Akaho, Elikplim H / Harris, Rebecca M / Congdon, Morgan / Korn, Emilie / Neher, Samuel / M'Farrej, Mirna / Burns, Julianne / Odom John, Audrey R

ACS infectious diseases

2021 Volume 7, Issue 9, Page(s) 2596–2603

Abstract: SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid noninvasive method to detect ... ...

Abstract	SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid noninvasive method to detect infection would be highly advantageous. Compelling evidence from canine biosensors and studies of adults with COVID-19 suggests that infection reproducibly alters human volatile organic compound (VOC) profiles. To determine whether pediatric infection is associated with VOC changes, we enrolled SARS-CoV-2 infected and uninfected children admitted to a major pediatric academic medical center. Breath samples were collected from children and analyzed through state-of-the-art GCxGC-ToFMS. Isolated features included 84 targeted VOCs. Candidate biomarkers that were correlated with infection status were subsequently validated in a second, independent cohort of children. We thus find that six volatile organic compounds are significantly and reproducibly increased in the breath of SARS-CoV-2 infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention, as aldehydes are also elevated in the breath of adults with COVID-19. Together, these biomarkers demonstrate high accuracy for distinguishing pediatric SARS-CoV-2 infection and support the ongoing development of novel breath-based diagnostics.
Language	English
Publishing date	2021-07-28
Publishing country	United States
Document type	Journal Article
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.1c00248
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Article: Reproducible breath metabolite changes in children with SARS-CoV-2 infection.

Berna, Amalia Z / Akaho, Elikplim H / Harris, Rebecca M / Congdon, Morgan / Korn, Emilie / Neher, Samuel / M'Farrej, Mirna / Burns, Julianne / John, Audrey R Odom

medRxiv : the preprint server for health sciences

2021

Abstract	SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid non-invasive method to detect infection would be highly advantageous. Compelling evidence from canine biosensors and studies of adults with COVID-19 suggests that infection reproducibly alters human volatile organic compounds (VOCs) profiles. To determine whether pediatric infection is associated with VOC changes, we enrolled SARS-CoV-2-infected and -uninfected children admitted to a major pediatric academic medical center. Breath samples were collected from children and analyzed through state-of-the-art GCxGC-ToFMS. Isolated features included 84 targeted VOCs. Candidate biomarkers that were correlated with infection status were subsequently validated in a second, independent cohort of children. We thus find that six volatile organic compounds are significantly and reproducibly increased in the breath of SARS-CoV-2-infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention, as aldehydes are also elevated in the breath of adults with COVID-19. Together, these biomarkers demonstrate high accuracy for distinguishing pediatric SARS-CoV-2 infection and support the ongoing development of novel breath-based diagnostics.
Language	English
Publishing date	2021-05-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.12.04.20230755
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