Pub Date : 2024-05-17DOI: 10.1088/1752-7163/ad4736
Barbora Czippelová, Slavomíra Nováková, Miroslava Šarlinová, Eva Baranovičová, Anna Urbanová, Zuzana Turianiková, Jana Čerňanová Krohová, Erika Halašová, Henrieta Škovierová
The analysis of volatile organic compounds (VOCs) in exhaled air has attracted the interest of the scientific community because it provides the possibility of monitoring physiological and metabolic processes and non-invasive diagnostics of various diseases. However, this method remains underused in clinical practice as well as in research because of the lack of standardized procedures for the collection, storage and transport of breath samples, which would guarantee good reproducibility and comparability of results. The method of sampling, as well as the storage time of the breath samples in the polymer bags used for sample storage and transport, affect the composition and concentration of VOCs present in the breath samples. The aim of our study was to compare breath samples obtained using two methods with fully disposable equipment: a Haldane sampling tube intended for direct breath collection and breath samples exhaled into a transparent Tedlar bag. The second task was to monitor the stability of selected compounds of real breath samples stored in a Tedlar bag for 6 h. Gas chromatography coupled with ion mobility spectrometry (GC-IMS) implemented in the BreathSpec®device was used to analyse exhaled breath. Our results showed a significant difference in the signal intensity of some volatiles when taking a breath sample with a Haldane tube and a Tedlar bag. Due to its endogenous origin, acetone levels were significantly higher when the Haldane tube sampler was used while elevated levels of 2-propanol and unidentified VOC (designated as VOC 3) in the Tedlar bag samples likely originated from contamination of the Tedlar bags. The VOC stability study revealed compound-specific signal intensity changes of the selected VOCs with storage time in the Tedlar bags, with some volatiles showing increasing signal intensity during storage in Tedlar bags. This limits the use of Tedlar bags only for very limited time and carefully selected purpose. Our results highlight the importance of careful design and implementation of experiments and clinical protocols to obtain relevant and reliable results.
{"title":"Impact of breath sample collection method and length of storage of breath samples in Tedlar bags on the level of selected volatiles assessed using gas chromatography-ion mobility spectrometry (GC-IMS).","authors":"Barbora Czippelová, Slavomíra Nováková, Miroslava Šarlinová, Eva Baranovičová, Anna Urbanová, Zuzana Turianiková, Jana Čerňanová Krohová, Erika Halašová, Henrieta Škovierová","doi":"10.1088/1752-7163/ad4736","DOIUrl":"10.1088/1752-7163/ad4736","url":null,"abstract":"<p><p>The analysis of volatile organic compounds (VOCs) in exhaled air has attracted the interest of the scientific community because it provides the possibility of monitoring physiological and metabolic processes and non-invasive diagnostics of various diseases. However, this method remains underused in clinical practice as well as in research because of the lack of standardized procedures for the collection, storage and transport of breath samples, which would guarantee good reproducibility and comparability of results. The method of sampling, as well as the storage time of the breath samples in the polymer bags used for sample storage and transport, affect the composition and concentration of VOCs present in the breath samples. The aim of our study was to compare breath samples obtained using two methods with fully disposable equipment: a Haldane sampling tube intended for direct breath collection and breath samples exhaled into a transparent Tedlar bag. The second task was to monitor the stability of selected compounds of real breath samples stored in a Tedlar bag for 6 h. Gas chromatography coupled with ion mobility spectrometry (GC-IMS) implemented in the BreathSpec<sup>®</sup>device was used to analyse exhaled breath. Our results showed a significant difference in the signal intensity of some volatiles when taking a breath sample with a Haldane tube and a Tedlar bag. Due to its endogenous origin, acetone levels were significantly higher when the Haldane tube sampler was used while elevated levels of 2-propanol and unidentified VOC (designated as VOC 3) in the Tedlar bag samples likely originated from contamination of the Tedlar bags. The VOC stability study revealed compound-specific signal intensity changes of the selected VOCs with storage time in the Tedlar bags, with some volatiles showing increasing signal intensity during storage in Tedlar bags. This limits the use of Tedlar bags only for very limited time and carefully selected purpose. Our results highlight the importance of careful design and implementation of experiments and clinical protocols to obtain relevant and reliable results.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-17DOI: 10.1088/1752-7163/ad48a9
Jonas Herth, Felix Schmidt, Sarah Basler, Noriane A Sievi, Malcolm Kohler
Exhaled breath analysis has emerged as a non-invasive and promising method for early detection of lung cancer, offering a novel approach for diagnosis through the identification of specific biomarkers present in a patient's breath. For this longitudinal study, 29 treatment-naive patients with lung cancer were evaluated before and after surgery. Secondary electrospray ionization high-resolution mass spectrometry was used for exhaled breath analysis. Volatile organic compounds with absolute log2fold change ⩾1 andq-values ⩾ 0.71 were selected as potentially relevant. Exhaled breath analysis resulted in a total of 3482 features. 515 features showed a substantial difference before and after surgery. The small sample size generated a false positive rate of 0.71, therefore, around 154 of these 515 features were expected to be true changes. Biological identification of the features with the highest consistency (m/z-242.18428 andm/z-117.0539) revealed to potentially be 3-Oxotetradecanoic acid and Indole, respectively. Principal component analysis revealed a primary cluster of patients with a recurrent lung cancer, which remained undetected in the initial diagnostic and surgical procedures. The change of exhaled breath patterns after surgery in lung cancer emphasizes the potential for lung cancer screening and detection.
{"title":"Exhaled breath analysis in patients with potentially curative lung cancer undergoing surgery: a longitudinal study.","authors":"Jonas Herth, Felix Schmidt, Sarah Basler, Noriane A Sievi, Malcolm Kohler","doi":"10.1088/1752-7163/ad48a9","DOIUrl":"10.1088/1752-7163/ad48a9","url":null,"abstract":"<p><p>Exhaled breath analysis has emerged as a non-invasive and promising method for early detection of lung cancer, offering a novel approach for diagnosis through the identification of specific biomarkers present in a patient's breath. For this longitudinal study, 29 treatment-naive patients with lung cancer were evaluated before and after surgery. Secondary electrospray ionization high-resolution mass spectrometry was used for exhaled breath analysis. Volatile organic compounds with absolute log<sup>2</sup>fold change ⩾1 and<i>q</i>-values ⩾ 0.71 were selected as potentially relevant. Exhaled breath analysis resulted in a total of 3482 features. 515 features showed a substantial difference before and after surgery. The small sample size generated a false positive rate of 0.71, therefore, around 154 of these 515 features were expected to be true changes. Biological identification of the features with the highest consistency (<i>m</i>/<i>z</i>-242.18428 and<i>m</i>/<i>z</i>-117.0539) revealed to potentially be 3-Oxotetradecanoic acid and Indole, respectively. Principal component analysis revealed a primary cluster of patients with a recurrent lung cancer, which remained undetected in the initial diagnostic and surgical procedures. The change of exhaled breath patterns after surgery in lung cancer emphasizes the potential for lung cancer screening and detection.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-25DOI: 10.1088/1752-7163/ad4388
P. Mochalski, J. King, K. Unterkofler, Christopher A. Mayhew
In the breath research community's search for volatile organic compounds that can act as non-invasive biomarkers for various diseases, hundreds of endogenous volatiles have been discovered. Whilst these systemic chemicals result from normal and abnormal metabolic activities or pathological disorders, to date very few are of any use for the development of clinical breath tests that could be used for disease diagnosis or to monitor therapeutic treatments. The reasons for this lack of application are manifold and complex, and these complications either limit or ultimately inhibit the analytical application of endogenous volatiles for use in the medical sciences. One such complication is a lack of knowledge on the biological origins of the endogenous volatiles. A major exception to this is isoprene. Since 1984, i.e., for forty years, it has been generally accepted that the pathway to the production of human isoprene, and hence the origin of isoprene in exhaled breath, is through cholesterol biosynthesis via the mevalonate (MVA) pathway within the liver. However, various studies between 2001 and 2012 provide compelling evidence that human isoprene is produced in skeletal muscle tissue. A recent multi-omic investigation of genes and metabolites has revealed that this proposal is correct by showing that human isoprene predominantly results from muscular lipolytic cholesterol metabolism. Despite the overwhelming proof for a muscular pathway to isoprene production in the human body, breath research papers still reference the hepatic MVA pathway. The major aim of this perspective is review the evidence that leads to a correct interpretation for the origins of human isoprene, so that the major pathway to human isoprene production is understood and appropriately disseminated. This is important, because an accurate attribution to the endogenous origins of isoprene is needed if exhaled isoprene levels are to be correctly interpreted and for assessing isoprene as a clinical biomarker.
{"title":"Unravelling the origin of isoprene in the human body - a forty year odyssey.","authors":"P. Mochalski, J. King, K. Unterkofler, Christopher A. Mayhew","doi":"10.1088/1752-7163/ad4388","DOIUrl":"https://doi.org/10.1088/1752-7163/ad4388","url":null,"abstract":"In the breath research community's search for volatile organic compounds that can act as non-invasive biomarkers for various diseases, hundreds of endogenous volatiles have been discovered. Whilst these systemic chemicals result from normal and abnormal metabolic activities or pathological disorders, to date very few are of any use for the development of clinical breath tests that could be used for disease diagnosis or to monitor therapeutic treatments. The reasons for this lack of application are manifold and complex, and these complications either limit or ultimately inhibit the analytical application of endogenous volatiles for use in the medical sciences. One such complication is a lack of knowledge on the biological origins of the endogenous volatiles. A major exception to this is isoprene. Since 1984, i.e., for forty years, it has been generally accepted that the pathway to the production of human isoprene, and hence the origin of isoprene in exhaled breath, is through cholesterol biosynthesis via the mevalonate (MVA) pathway within the liver. However, various studies between 2001 and 2012 provide compelling evidence that human isoprene is produced in skeletal muscle tissue. A recent multi-omic investigation of genes and metabolites has revealed that this proposal is correct by showing that human isoprene predominantly results from muscular lipolytic cholesterol metabolism. Despite the overwhelming proof for a muscular pathway to isoprene production in the human body, breath research papers still reference the hepatic MVA pathway. The major aim of this perspective is review the evidence that leads to a correct interpretation for the origins of human isoprene, so that the major pathway to human isoprene production is understood and appropriately disseminated. This is important, because an accurate attribution to the endogenous origins of isoprene is needed if exhaled isoprene levels are to be correctly interpreted and for assessing isoprene as a clinical biomarker.","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.1088/1752-7163/ad3fde
Ophir Bar-On, Ori Goldberg, P. Stafler, H. Levine, Eyal Jacobi, Einat Shmueli, Benjamin Rothschild, D. Prais, M. Mei-Zahav
BACKGROUND During the COVID-19 pandemic wearing face masks was mandatory. Nowadays, face masks are still encouraged indoors, especially in hospitals. People climbing stairs with masks describe unpredictable dyspnea. Methods: Healthy adults climbed 5 floors with and without a mask. Various cardio-respiratory parameters were measured, including O2-Saturation (O2-Sat) and End-tidal CO2 (EtCO2), at baseline and on the top floor. Subjective indexes, such as Borg's scale, were evaluated. Results: Thirty-two volunteers (16 males), median age 39 years (IQR 32.5-43), median BMI=23.6 (IQR 21.5-25.1), with good fitness levels, participated. Comparing baseline to end-activity, median (IQR): O2-Sat change was -1.0% (-2-0) without mask, versus -3.0% (-4-0) with mask, p=0.003; EtCO2 +7.0 (+3.3-+9) without mask, versus +8.0 (+6 -+12) with mask, p=0.0001. Hypercarbia was seen in 5 (15.6%) participants without mask, median=48mmHg (IQR 47.5-51), and in 11 (34%) participants with mask, median=50mmHg (IQR 47-54), p<0.001. Desaturation (O2-Sat<95%) was seen in 5 (15.6%) participants without mask, median=94% (IQR 93-94%), and in 10 (31%) participants with mask, median=91.5% (IQR 90-93%), p=0.06. Regression analysis demonstrated that only male sex was significantly associated with abnormal EtCO2 (OR=26.4, 95%CI=1.9-366.4, p=0.005). Ascent duration increased from median (IQR) of 94 seconds (86-100) without mask to 98 seconds (89-107) with mask, p<0.001. Borg's scale of perceived exertion (range 0-10) increased from median (IQR) of 3.0 (2.5-3.87) without mask to 4.0 (3.0-4.37) with mask, p<0.001. Conclusions: During routine daily activities, such as stair-climbing, face masks cause dyspnea, and have measurable influences on ventilation, including true desaturation and hypercapnia, especially in males. .
{"title":"Wearing face masks while climbing stairs influences respiratory physiology.","authors":"Ophir Bar-On, Ori Goldberg, P. Stafler, H. Levine, Eyal Jacobi, Einat Shmueli, Benjamin Rothschild, D. Prais, M. Mei-Zahav","doi":"10.1088/1752-7163/ad3fde","DOIUrl":"https://doi.org/10.1088/1752-7163/ad3fde","url":null,"abstract":"BACKGROUND\u0000During the COVID-19 pandemic wearing face masks was mandatory. Nowadays, face masks are still encouraged indoors, especially in hospitals. People climbing stairs with masks describe unpredictable dyspnea. Methods: Healthy adults climbed 5 floors with and without a mask. Various cardio-respiratory parameters were measured, including O2-Saturation (O2-Sat) and End-tidal CO2 (EtCO2), at baseline and on the top floor. Subjective indexes, such as Borg's scale, were evaluated. Results: Thirty-two volunteers (16 males), median age 39 years (IQR 32.5-43), median BMI=23.6 (IQR 21.5-25.1), with good fitness levels, participated. Comparing baseline to end-activity, median (IQR): O2-Sat change was -1.0% (-2-0) without mask, versus -3.0% (-4-0) with mask, p=0.003; EtCO2 +7.0 (+3.3-+9) without mask, versus +8.0 (+6 -+12) with mask, p=0.0001. Hypercarbia was seen in 5 (15.6%) participants without mask, median=48mmHg (IQR 47.5-51), and in 11 (34%) participants with mask, median=50mmHg (IQR 47-54), p<0.001. Desaturation (O2-Sat<95%) was seen in 5 (15.6%) participants without mask, median=94% (IQR 93-94%), and in 10 (31%) participants with mask, median=91.5% (IQR 90-93%), p=0.06. Regression analysis demonstrated that only male sex was significantly associated with abnormal EtCO2 (OR=26.4, 95%CI=1.9-366.4, p=0.005). Ascent duration increased from median (IQR) of 94 seconds (86-100) without mask to 98 seconds (89-107) with mask, p<0.001. Borg's scale of perceived exertion (range 0-10) increased from median (IQR) of 3.0 (2.5-3.87) without mask to 4.0 (3.0-4.37) with mask, p<0.001. Conclusions: During routine daily activities, such as stair-climbing, face masks cause dyspnea, and have measurable influences on ventilation, including true desaturation and hypercapnia, especially in males. .","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140690580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.1088/1752-7163/ad3fdf
Hsuan Chou, Lucy Godbeer, Madeleine Ball
The annual Breath Biopsy Conference hosted by Owlstone Medical gathers together the leading experts, early career researchers, and physicians working with breath as a biomarker platform for clinical purposes. The current topics in breath research are discussed and presented, and an overarching topical theme is identified and discussed as part of an expert panel to close the conference. The profiling of normal breath composition and the establishment of standards for analyzing breath compared to background signal were two important topics that were major focuses of this conference, as well as important innovative progress that has been made since last year, including the development of a non-invasive breath test for lung cancer and liver disease. This meeting report offers an overview of the key take-home messages from the various presentations, posters, and discussions from the conference.
{"title":"Establishing Breath as a Biomarker Platform - Take Home Messages from the Breath Biopsy Conference 2023.","authors":"Hsuan Chou, Lucy Godbeer, Madeleine Ball","doi":"10.1088/1752-7163/ad3fdf","DOIUrl":"https://doi.org/10.1088/1752-7163/ad3fdf","url":null,"abstract":"The annual Breath Biopsy Conference hosted by Owlstone Medical gathers together the leading experts, early career researchers, and physicians working with breath as a biomarker platform for clinical purposes. The current topics in breath research are discussed and presented, and an overarching topical theme is identified and discussed as part of an expert panel to close the conference. The profiling of normal breath composition and the establishment of standards for analyzing breath compared to background signal were two important topics that were major focuses of this conference, as well as important innovative progress that has been made since last year, including the development of a non-invasive breath test for lung cancer and liver disease. This meeting report offers an overview of the key take-home messages from the various presentations, posters, and discussions from the conference.","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140694198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1088/1752-7163/ad38d5
Julia Eichinger, Anna-Maria Reiche, Frigga Dohme-Meier, Pascal Fuchsmann
We explored appropriate technical setups for the detection of volatile organic compounds (VOCs) from exhaled cow breath by comparing six different polymer-based solid-phase extraction (SPE) cartridges currently on the market for gas chromatography/mass spectrometry (GC-MS) screening. Exhaled breath was sampled at a single timepoint from five lactating dairy cows using six different SPE cartridges (Bond Elut ENV (ENV); Chromabond HRX (HRX); Chromabond HRP (HRP); Chromabond HLB (HLB); Chromabond HR-XCW (XCW) and Chromabond HR-XAW (XAW)). The trapped VOCs were analyzed by dynamic headspace vacuum in-tube extraction GC-MS (DHS-V-ITEX-GC-MS). Depending on the SPE cartridge, we detected 1174-1312 VOCs per cartridge. Most VOCs were alkenes, alkanes, esters, ketones, alcohols, aldehydes, amines, nitriles, ethers, amides, carboxylic acids, alkynes, azoles, terpenes, pyridines, or sulfur-containing compounds. The six SPE cartridges differed in their specificity for the chemical compounds, with the XAW cartridge showing the best specificity for ketones. The greatest differences between the tested SPE cartridges appeared in the detection of specific VOCs. In total, 176 different VOCs were detected with a match factor >80%. The greatest number of specific VOCs was captured by XAW (149), followed by ENV (118), HLB (117), HRP (115), HRX (114), and XCW (114). We conclude that the tested SPE cartridges are suitable for VOC sampling from exhaled cow breath, but the SPE cartridge choice enormously affects the detected chemical groups and the number of detected VOCs. Therefore, an appropriate SPE adsorbent cartridge should be selected according to our proposed inclusion criteria. For targeted metabolomics approaches, the SPE cartridge choice depends on the VOCs or chemical compound groups of interest based on our provided VOC list. For untargeted approaches without information on the animals' metabolic condition, we suggest using multi-sorbent SPE cartridges or multiple cartridges per animal.
{"title":"Optimization of volatile organic compounds sampling from dairy cow exhaled breath using polymer-based solid-phase extraction cartridges for gas chromatographic analysis.","authors":"Julia Eichinger, Anna-Maria Reiche, Frigga Dohme-Meier, Pascal Fuchsmann","doi":"10.1088/1752-7163/ad38d5","DOIUrl":"10.1088/1752-7163/ad38d5","url":null,"abstract":"<p><p>We explored appropriate technical setups for the detection of volatile organic compounds (VOCs) from exhaled cow breath by comparing six different polymer-based solid-phase extraction (SPE) cartridges currently on the market for gas chromatography/mass spectrometry (GC-MS) screening. Exhaled breath was sampled at a single timepoint from five lactating dairy cows using six different SPE cartridges (Bond Elut ENV (ENV); Chromabond HRX (HRX); Chromabond HRP (HRP); Chromabond HLB (HLB); Chromabond HR-XCW (XCW) and Chromabond HR-XAW (XAW)). The trapped VOCs were analyzed by dynamic headspace vacuum in-tube extraction GC-MS (DHS-V-ITEX-GC-MS). Depending on the SPE cartridge, we detected 1174-1312 VOCs per cartridge. Most VOCs were alkenes, alkanes, esters, ketones, alcohols, aldehydes, amines, nitriles, ethers, amides, carboxylic acids, alkynes, azoles, terpenes, pyridines, or sulfur-containing compounds. The six SPE cartridges differed in their specificity for the chemical compounds, with the XAW cartridge showing the best specificity for ketones. The greatest differences between the tested SPE cartridges appeared in the detection of specific VOCs. In total, 176 different VOCs were detected with a match factor >80%. The greatest number of specific VOCs was captured by XAW (149), followed by ENV (118), HLB (117), HRP (115), HRX (114), and XCW (114). We conclude that the tested SPE cartridges are suitable for VOC sampling from exhaled cow breath, but the SPE cartridge choice enormously affects the detected chemical groups and the number of detected VOCs. Therefore, an appropriate SPE adsorbent cartridge should be selected according to our proposed inclusion criteria. For targeted metabolomics approaches, the SPE cartridge choice depends on the VOCs or chemical compound groups of interest based on our provided VOC list. For untargeted approaches without information on the animals' metabolic condition, we suggest using multi-sorbent SPE cartridges or multiple cartridges per animal.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28DOI: 10.1088/1752-7163/ad3572
Teny M John, Nabin K Shrestha, Leen Hasan, Kirk Pappan, Owen Birch, David Grove, Billy Boyle, Max Allsworth, Priyanka Shrestha, Gary W Procop, Raed A Dweik
Clostridioides difficileinfection (CDI) is the leading cause of hospital-acquired infective diarrhea. Current methods for diagnosing CDI have limitations; enzyme immunoassays for toxin have low sensitivity andClostridioides difficilepolymerase chain reaction cannot differentiate infection from colonization. An ideal diagnostic test that incorporates microbial factors, host factors, and host-microbe interaction might characterize true infection. Assessing volatile organic compounds (VOCs) in exhaled breath may be a useful test for identifying CDI. To identify a wide selection of VOCs in exhaled breath, we used thermal desorption-gas chromatography-mass spectrometry to study breath samples from 17 patients with CDI. Age- and sex-matched patients with diarrhea and negativeC.difficiletesting (no CDI) were used as controls. Of the 65 VOCs tested, 9 were used to build a quadratic discriminant model that showed a final cross-validated accuracy of 74%, a sensitivity of 71%, a specificity of 76%, and a receiver operating characteristic area under the curve of 0.72. If these findings are proven by larger studies, breath VOC analysis may be a helpful adjunctive diagnostic test for CDI.
{"title":"Detection of<i>Clostridioides difficile</i>infection by assessment of exhaled breath volatile organic compounds.","authors":"Teny M John, Nabin K Shrestha, Leen Hasan, Kirk Pappan, Owen Birch, David Grove, Billy Boyle, Max Allsworth, Priyanka Shrestha, Gary W Procop, Raed A Dweik","doi":"10.1088/1752-7163/ad3572","DOIUrl":"10.1088/1752-7163/ad3572","url":null,"abstract":"<p><p><i>Clostridioides difficile</i>infection (CDI) is the leading cause of hospital-acquired infective diarrhea. Current methods for diagnosing CDI have limitations; enzyme immunoassays for toxin have low sensitivity and<i>Clostridioides difficile</i>polymerase chain reaction cannot differentiate infection from colonization. An ideal diagnostic test that incorporates microbial factors, host factors, and host-microbe interaction might characterize true infection. Assessing volatile organic compounds (VOCs) in exhaled breath may be a useful test for identifying CDI. To identify a wide selection of VOCs in exhaled breath, we used thermal desorption-gas chromatography-mass spectrometry to study breath samples from 17 patients with CDI. Age- and sex-matched patients with diarrhea and negative<i>C.difficile</i>testing (no CDI) were used as controls. Of the 65 VOCs tested, 9 were used to build a quadratic discriminant model that showed a final cross-validated accuracy of 74%, a sensitivity of 71%, a specificity of 76%, and a receiver operating characteristic area under the curve of 0.72. If these findings are proven by larger studies, breath VOC analysis may be a helpful adjunctive diagnostic test for CDI.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-21DOI: 10.1088/1752-7163/ad324f
Linda Mezmale, Daria Ślefarska-Wolak, Manohar Prasad Bhandari, Clemens Ager, Viktors Veliks, Veronika Patsko, Andrii Lukashenko, Emmanuel Dias-Neto, Diana Noronha Nunes, Thais Fernanda Bartelli, Adriane Graicer Pelosof, Claudia Zitron Sztokfisz, Raúl Murillo, Agnieszka Królicka, Chris A Mayhew, Marcis Leja, Hossam Haick, Pawel Mochalski
Volatilomics is a powerful tool capable of providing novel biomarkers for the diagnosis of gastric cancer. The main objective of this study was to characterize the volatilomic signatures of gastric juice in order to identify potential alterations induced by gastric cancer. Gas chromatography with mass spectrometric detection, coupled with headspace solid phase microextraction as the pre-concentration technique, was used to identify volatile organic compounds (VOCs) released by gastric juice samples collected from 78 gastric cancer patients and two cohorts of controls (80 and 96 subjects) from four different locations (Latvia, Ukraine, Brazil, and Colombia). 1440 distinct compounds were identified in samples obtained from patients and 1422 in samples provided by controls. However, only 6% of the VOCs exhibited an incidence higher than 20%. Amongst the volatiles emitted, 18 showed differences in their headspace concentrations above gastric juice of cancer patients and controls. Ten of these (1-propanol, 2,3-butanedione, 2-pentanone, benzeneacetaldehyde, 3-methylbutanal, butylated hydroxytoluene, 2-pentyl-furan, 2-ethylhexanal, 2-methylpropanal and phenol) appeared at significantly higher levels in the headspace of the gastric juice samples obtained from patients; whereas, eight species showed lower abundance in patients than found in controls. Given that the difference in the volatilomic signatures can be explained by cancer-related changes in the activity of certain enzymes or pathways, the former set can be considered potential biomarkers for gastric cancer, which may assist in developing non-invasive breath tests for the diagnosis of this disease. Further studies are required to elucidate further the mechanisms that underlie the changes in the volatilomic profile as a result of gastric cancer.
{"title":"Volatilomic profiles of gastric juice in gastric cancer patients.","authors":"Linda Mezmale, Daria Ślefarska-Wolak, Manohar Prasad Bhandari, Clemens Ager, Viktors Veliks, Veronika Patsko, Andrii Lukashenko, Emmanuel Dias-Neto, Diana Noronha Nunes, Thais Fernanda Bartelli, Adriane Graicer Pelosof, Claudia Zitron Sztokfisz, Raúl Murillo, Agnieszka Królicka, Chris A Mayhew, Marcis Leja, Hossam Haick, Pawel Mochalski","doi":"10.1088/1752-7163/ad324f","DOIUrl":"10.1088/1752-7163/ad324f","url":null,"abstract":"<p><p>Volatilomics is a powerful tool capable of providing novel biomarkers for the diagnosis of gastric cancer. The main objective of this study was to characterize the volatilomic signatures of gastric juice in order to identify potential alterations induced by gastric cancer. Gas chromatography with mass spectrometric detection, coupled with headspace solid phase microextraction as the pre-concentration technique, was used to identify volatile organic compounds (VOCs) released by gastric juice samples collected from 78 gastric cancer patients and two cohorts of controls (80 and 96 subjects) from four different locations (Latvia, Ukraine, Brazil, and Colombia). 1440 distinct compounds were identified in samples obtained from patients and 1422 in samples provided by controls. However, only 6% of the VOCs exhibited an incidence higher than 20%. Amongst the volatiles emitted, 18 showed differences in their headspace concentrations above gastric juice of cancer patients and controls. Ten of these (1-propanol, 2,3-butanedione, 2-pentanone, benzeneacetaldehyde, 3-methylbutanal, butylated hydroxytoluene, 2-pentyl-furan, 2-ethylhexanal, 2-methylpropanal and phenol) appeared at significantly higher levels in the headspace of the gastric juice samples obtained from patients; whereas, eight species showed lower abundance in patients than found in controls. Given that the difference in the volatilomic signatures can be explained by cancer-related changes in the activity of certain enzymes or pathways, the former set can be considered potential biomarkers for gastric cancer, which may assist in developing non-invasive breath tests for the diagnosis of this disease. Further studies are required to elucidate further the mechanisms that underlie the changes in the volatilomic profile as a result of gastric cancer.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-13DOI: 10.1088/1752-7163/ad2b6e
Ruth P Cusack, Robyn Larracy, Christian B Morrell, Maral Ranjbar, Jennifer Le Roux, Christiane E Whetstone, Maxime Boudreau, Patrick F Poitras, Thiviya Srinathan, Eric Cheng, Karen Howie, Catie Obminski, Tim O'Shea, Rebecca J Kruisselbrink, Terence Ho, Erik Scheme, Stephen Graham, Gisia Beydaghyan, Gail M Gavreau, MyLinh Duong
Detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) relies on real-time-reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. The false-negative rate of RT-PCR can be high when viral burden and infection is localized distally in the lower airways and lung parenchyma. An alternate safe, simple and accessible method for sampling the lower airways is needed to aid in the early and rapid diagnosis of COVID-19 pneumonia. In a prospective unblinded observational study, patients admitted with a positive RT-PCR and symptoms of SARS-CoV-2 infection were enrolled from three hospitals in Ontario, Canada. Healthy individuals or hospitalized patients with negative RT-PCR and without respiratory symptoms were enrolled into the control group. Breath samples were collected and analyzed by laser absorption spectroscopy (LAS) for volatile organic compounds (VOCs) and classified by machine learning (ML) approaches to identify unique LAS-spectra patterns (breathprints) for SARS-CoV-2. Of the 135 patients enrolled, 115 patients provided analyzable breath samples. Using LAS-breathprints to train ML classifier models resulted in an accuracy of 72.2%-81.7% in differentiating between SARS-CoV2 positive and negative groups. The performance was consistent across subgroups of different age, sex, body mass index, SARS-CoV-2 variants, time of disease onset and oxygen requirement. The overall performance was higher than compared to VOC-trained classifier model, which had an accuracy of 63%-74.7%. This study demonstrates that a ML-based breathprint model using LAS analysis of exhaled breath may be a valuable non-invasive method for studying the lower airways and detecting SARS-CoV-2 and other respiratory pathogens. The technology and the ML approach can be easily deployed in any setting with minimal training. This will greatly improve access and scalability to meet surge capacity; allow early and rapid detection to inform therapy; and offers great versatility in developing new classifier models quickly for future outbreaks.
背景
严重急性呼吸系统综合症冠状病毒-2(SARS-CoV-2)的检测依赖于鼻咽拭子上的实时逆转录酶聚合酶链反应(RT-PCR)。当病毒负荷和感染位于下呼吸道和肺实质的远端时,RT-PCR 的假阴性率会很高。我们需要一种安全、简单、方便的下呼吸道取样方法,以帮助早期快速诊断 COVID-19 肺炎。健康人或 RT-PCR 阴性且无呼吸道症状的住院患者被纳入对照组。收集的呼吸样本通过激光吸收光谱 (LAS) 分析挥发性有机化合物 (VOC),并通过机器学习 (ML) 方法进行分类,以识别 SARS-CoV-2 的独特 LAS 光谱模式(呼吸样本)。使用 LAS 呼吸指纹训练 ML 分类器模型,在区分 SARS-CoV2 阳性组和阴性组方面的准确率为 72-2-81-7%。在不同年龄、性别、体重指数、SARS-CoV-2 变体、发病时间和需氧量的亚组中,准确率保持一致。总体性能高于 VOC 训练的分类器模型,后者的准确率为 63-74-7%。该技术和 ML 方法只需少量培训即可在任何环境中轻松部署。这将极大地提高可及性和可扩展性,以满足激增的容量;允许早期和快速检测,为治疗提供信息;并为快速开发新的分类器模型以应对未来的爆发提供了极大的通用性。
{"title":"Machine learning enabled detection of COVID-19 pneumonia using exhaled breath analysis: a proof-of-concept study.","authors":"Ruth P Cusack, Robyn Larracy, Christian B Morrell, Maral Ranjbar, Jennifer Le Roux, Christiane E Whetstone, Maxime Boudreau, Patrick F Poitras, Thiviya Srinathan, Eric Cheng, Karen Howie, Catie Obminski, Tim O'Shea, Rebecca J Kruisselbrink, Terence Ho, Erik Scheme, Stephen Graham, Gisia Beydaghyan, Gail M Gavreau, MyLinh Duong","doi":"10.1088/1752-7163/ad2b6e","DOIUrl":"10.1088/1752-7163/ad2b6e","url":null,"abstract":"<p><p>Detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) relies on real-time-reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. The false-negative rate of RT-PCR can be high when viral burden and infection is localized distally in the lower airways and lung parenchyma. An alternate safe, simple and accessible method for sampling the lower airways is needed to aid in the early and rapid diagnosis of COVID-19 pneumonia. In a prospective unblinded observational study, patients admitted with a positive RT-PCR and symptoms of SARS-CoV-2 infection were enrolled from three hospitals in Ontario, Canada. Healthy individuals or hospitalized patients with negative RT-PCR and without respiratory symptoms were enrolled into the control group. Breath samples were collected and analyzed by laser absorption spectroscopy (LAS) for volatile organic compounds (VOCs) and classified by machine learning (ML) approaches to identify unique LAS-spectra patterns (breathprints) for SARS-CoV-2. Of the 135 patients enrolled, 115 patients provided analyzable breath samples. Using LAS-breathprints to train ML classifier models resulted in an accuracy of 72.2%-81.7% in differentiating between SARS-CoV2 positive and negative groups. The performance was consistent across subgroups of different age, sex, body mass index, SARS-CoV-2 variants, time of disease onset and oxygen requirement. The overall performance was higher than compared to VOC-trained classifier model, which had an accuracy of 63%-74.7%. This study demonstrates that a ML-based breathprint model using LAS analysis of exhaled breath may be a valuable non-invasive method for studying the lower airways and detecting SARS-CoV-2 and other respiratory pathogens. The technology and the ML approach can be easily deployed in any setting with minimal training. This will greatly improve access and scalability to meet surge capacity; allow early and rapid detection to inform therapy; and offers great versatility in developing new classifier models quickly for future outbreaks.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-12DOI: 10.1088/1752-7163/ad23f5
Hsuan Chou, Kayleigh Arthur, Elen Shaw, Chad Schaber, Billy Boyle, Max Allsworth, Eli F Kelley, Glenn M Stewart, Courtney M Wheatley, Jesse Schwartz, Caitlin C Fermoyle, Briana L Ziegler, Kay A Johnson, Paul Robach, Patrick Basset, Bruce D Johnson
Exhaustive exercise can induce unique physiological responses in the lungs and other parts of the human body. The volatile organic compounds (VOCs) in exhaled breath are ideal for studying the effects of exhaustive exercise on the lungs due to the proximity of the breath matrix to the respiratory tract. As breath VOCs can originate from the bloodstream, changes in abundance should also indicate broader physiological effects of exhaustive exercise on the body. Currently, there is limited published data on the effects of exhaustive exercise on breath VOCs. Breath has great potential for biomarker analysis as it can be collected non-invasively, and capture real-time metabolic changes to better understand the effects of exhaustive exercise. In this study, we collected breath samples from a small group of elite runners participating in the 2019 Ultra-Trail du Mont Blanc ultra-marathon. The final analysis included matched paired samples collected before and after the race from 24 subjects. All 48 samples were analyzed using the Breath Biopsy Platform with GC-Orbitrap™ via thermal desorption gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to determine whether VOC abundances differed between pre- and post-race breath samples (adjustedP-value < .05). We identified a total of 793 VOCs in the breath samples of elite runners. Of these, 63 showed significant differences between pre- and post-race samples after correction for multiple testing (12 decreased, 51 increased). The specific VOCs identified suggest the involvement of fatty acid oxidation, inflammation, and possible altered gut microbiome activity in response to exhaustive exercise. This study demonstrates significant changes in VOC abundance resulting from exhaustive exercise. Further investigation of VOC changes along with other physiological measurements can help improve our understanding of the effect of exhaustive exercise on the body and subsequent differences in VOCs in exhaled breath.
{"title":"Metabolic insights at the finish line: deciphering physiological changes in ultramarathon runners through breath VOC analysis.","authors":"Hsuan Chou, Kayleigh Arthur, Elen Shaw, Chad Schaber, Billy Boyle, Max Allsworth, Eli F Kelley, Glenn M Stewart, Courtney M Wheatley, Jesse Schwartz, Caitlin C Fermoyle, Briana L Ziegler, Kay A Johnson, Paul Robach, Patrick Basset, Bruce D Johnson","doi":"10.1088/1752-7163/ad23f5","DOIUrl":"10.1088/1752-7163/ad23f5","url":null,"abstract":"<p><p>Exhaustive exercise can induce unique physiological responses in the lungs and other parts of the human body. The volatile organic compounds (VOCs) in exhaled breath are ideal for studying the effects of exhaustive exercise on the lungs due to the proximity of the breath matrix to the respiratory tract. As breath VOCs can originate from the bloodstream, changes in abundance should also indicate broader physiological effects of exhaustive exercise on the body. Currently, there is limited published data on the effects of exhaustive exercise on breath VOCs. Breath has great potential for biomarker analysis as it can be collected non-invasively, and capture real-time metabolic changes to better understand the effects of exhaustive exercise. In this study, we collected breath samples from a small group of elite runners participating in the 2019 Ultra-Trail du Mont Blanc ultra-marathon. The final analysis included matched paired samples collected before and after the race from 24 subjects. All 48 samples were analyzed using the Breath Biopsy Platform with GC-Orbitrap™ via thermal desorption gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to determine whether VOC abundances differed between pre- and post-race breath samples (adjusted<i>P</i>-value < .05). We identified a total of 793 VOCs in the breath samples of elite runners. Of these, 63 showed significant differences between pre- and post-race samples after correction for multiple testing (12 decreased, 51 increased). The specific VOCs identified suggest the involvement of fatty acid oxidation, inflammation, and possible altered gut microbiome activity in response to exhaustive exercise. This study demonstrates significant changes in VOC abundance resulting from exhaustive exercise. Further investigation of VOC changes along with other physiological measurements can help improve our understanding of the effect of exhaustive exercise on the body and subsequent differences in VOCs in exhaled breath.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}