Pub Date : 2023-09-25DOI: 10.1088/1752-7163/acf607
Andreas Kofoed, Mathias Hindborg, Jeppe Hjembæk-Brandt, Christian Dalby Sørensen, Mette Kolpen, Morten H Bestle
It can be a clinical challenge to distinguish inflammation from infection in critically ill patients. Therefore, valid and conclusive surrogate markers for infections are desired. Nitric oxide (NO) might be that marker since concentrations of exhaled NO have shown to change in the presence of various diseases. This observational, prospective, single-center feasibility study aimed to investigate if fractional exhaled NO (FeNO) can be measured in intubated patients with or without infection, pneumonia and septic shock in a standardized, reliable setting. 20 intubated patients in the intensive care unit (ICU) were included for analysis. FeNO mean values were measured in the endotracheal tube via the suction channel using a chemiluminescence based analyzer. We developed a pragmatic method to measure FeNO repeatedly and reliably in intubated patients using a chemiluminescence based analyzer. We found a median of 0.98 (0.59-1.44) FeNO mean (ppb) in exhaled breath from all 20 intubated patient. Intubated patient with suspected infection had a significantly lower median FeNO mean compared with the intubated patients without suspected infection. Similarly did patients with septic shock demonstrate a significantly lower median FeNO mean than without septic shock. We found no statistical difference in median FeNO mean for intubated patients with pneumonia. It was feasible to measure FeNO in intubated patients in the ICU. Our results indicate decreased levels of FeNO in infected intubated patients in the ICU. The study was not powered to provide firm conclusions, so larger trials are needed to confirm the results and to prove FeNO as a useful biomarker for distinguishment between infection and inflammation in the ICU.
{"title":"Exhaled nitric oxide in intubated ICU patients on mechanical ventilation-a feasibility study.","authors":"Andreas Kofoed, Mathias Hindborg, Jeppe Hjembæk-Brandt, Christian Dalby Sørensen, Mette Kolpen, Morten H Bestle","doi":"10.1088/1752-7163/acf607","DOIUrl":"10.1088/1752-7163/acf607","url":null,"abstract":"<p><p>It can be a clinical challenge to distinguish inflammation from infection in critically ill patients. Therefore, valid and conclusive surrogate markers for infections are desired. Nitric oxide (NO) might be that marker since concentrations of exhaled NO have shown to change in the presence of various diseases. This observational, prospective, single-center feasibility study aimed to investigate if fractional exhaled NO (FeNO) can be measured in intubated patients with or without infection, pneumonia and septic shock in a standardized, reliable setting. 20 intubated patients in the intensive care unit (ICU) were included for analysis. FeNO mean values were measured in the endotracheal tube via the suction channel using a chemiluminescence based analyzer. We developed a pragmatic method to measure FeNO repeatedly and reliably in intubated patients using a chemiluminescence based analyzer. We found a median of 0.98 (0.59-1.44) FeNO mean (ppb) in exhaled breath from all 20 intubated patient. Intubated patient with suspected infection had a significantly lower median FeNO mean compared with the intubated patients without suspected infection. Similarly did patients with septic shock demonstrate a significantly lower median FeNO mean than without septic shock. We found no statistical difference in median FeNO mean for intubated patients with pneumonia. It was feasible to measure FeNO in intubated patients in the ICU. Our results indicate decreased levels of FeNO in infected intubated patients in the ICU. The study was not powered to provide firm conclusions, so larger trials are needed to confirm the results and to prove FeNO as a useful biomarker for distinguishment between infection and inflammation in the ICU.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10511031","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 : 2023-09-21DOI: 10.1088/1752-7163/acf7e3
Kathleen Zwijsen, Eline Schillebeeckx, Eline Janssens, Joris Van Cleemput, Tom Richart, Veerle F Surmont, Kristiaan Nackaerts, Elly Marcq, Jan P van Meerbeeck, Kevin Lamote
Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the 'test, re-test' principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).
{"title":"Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results.","authors":"Kathleen Zwijsen, Eline Schillebeeckx, Eline Janssens, Joris Van Cleemput, Tom Richart, Veerle F Surmont, Kristiaan Nackaerts, Elly Marcq, Jan P van Meerbeeck, Kevin Lamote","doi":"10.1088/1752-7163/acf7e3","DOIUrl":"10.1088/1752-7163/acf7e3","url":null,"abstract":"<p><p>Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the 'test, re-test' principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10188837","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 : 2023-09-19DOI: 10.1088/1752-7163/acf782
Mo Awchi, Kapil Dev Singh, Patricia E Dill, Urs Frey, Alexandre N Datta, Pablo Sinues
Therapeutic drug monitoring (TDM) of medications with a narrow therapeutic window is a common clinical practice to minimize toxic effects and maximize clinical outcomes. Routine analyses rely on the quantification of systemic blood concentrations of drugs. Alternative matrices such as exhaled breath are appealing because of their inherent non-invasive nature. This is especially the case for pediatric patients. We have recently showcased the possibility of predicting systemic concentrations of valproic acid (VPA), an anti-seizure medication by real-time breath analysis in two real clinical settings. This approach, however, comes with the limitation of the patients having to physically exhale into the mass spectrometer. This restricts the possibility of sampling from patients not capable or available to exhale into the mass spectrometer located on the hospital premises. In this work, we developed an alternative method to overcome this limitation by collecting the breath samples in customized bags and subsequently analyzing them by secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS). A total ofn= 40 patients (mean ± SD, 11.5 ± 3.5 y.o.) diagnosed with epilepsy and taking VPA were included in this study. The patients underwent three measurements: (i) serum concentrations of total and free VPA, (ii) real-time breath analysis and (iii) off-line analysis of exhaled breath collected in bags. The agreement between the real-time and the off-line breath analysis methods was evaluated using Lin's concordance correlation coefficient (CCC). CCC was computed for ten mass spectral predictors of VPA concentrations. Lin's CCC was >0.6 for all VPA-associated features, except for two low-signal intensity isotopic peaks. Finally, free and total serum VPA concentrations were predicted by cross validating the off-line data set. Support vector machine algorithms provided the most accurate predictions with a root mean square error of cross validation of 29.0 ± 7.4 mg l-1and 3.9 ± 1.4 mg l-1for total and free VPA (mean ± SD), respectively. As a secondary analysis, we explored whether exhaled metabolites previously associated with side-effects and response to medication could be rendered by the off-line analysis method. We found that five features associated with side effects showed a CCC > 0.6, whereas none of the drug response-associated peaks reached this cut-off. We conclude that the clinically relevant free fraction of VPA can be predicted by this combination of off-line breath collection with rapid SESI-HRMS analysis. This opens new possibilities for breath based TDM in clinical settings.
{"title":"Prediction of systemic free and total valproic acid by off-line analysis of exhaled breath in epileptic children and adolescents.","authors":"Mo Awchi, Kapil Dev Singh, Patricia E Dill, Urs Frey, Alexandre N Datta, Pablo Sinues","doi":"10.1088/1752-7163/acf782","DOIUrl":"10.1088/1752-7163/acf782","url":null,"abstract":"<p><p>Therapeutic drug monitoring (TDM) of medications with a narrow therapeutic window is a common clinical practice to minimize toxic effects and maximize clinical outcomes. Routine analyses rely on the quantification of systemic blood concentrations of drugs. Alternative matrices such as exhaled breath are appealing because of their inherent non-invasive nature. This is especially the case for pediatric patients. We have recently showcased the possibility of predicting systemic concentrations of valproic acid (VPA), an anti-seizure medication by real-time breath analysis in two real clinical settings. This approach, however, comes with the limitation of the patients having to physically exhale into the mass spectrometer. This restricts the possibility of sampling from patients not capable or available to exhale into the mass spectrometer located on the hospital premises. In this work, we developed an alternative method to overcome this limitation by collecting the breath samples in customized bags and subsequently analyzing them by secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS). A total of<i>n</i>= 40 patients (mean ± SD, 11.5 ± 3.5 y.o.) diagnosed with epilepsy and taking VPA were included in this study. The patients underwent three measurements: (i) serum concentrations of total and free VPA, (ii) real-time breath analysis and (iii) off-line analysis of exhaled breath collected in bags. The agreement between the real-time and the off-line breath analysis methods was evaluated using Lin's concordance correlation coefficient (CCC). CCC was computed for ten mass spectral predictors of VPA concentrations. Lin's CCC was >0.6 for all VPA-associated features, except for two low-signal intensity isotopic peaks. Finally, free and total serum VPA concentrations were predicted by cross validating the off-line data set. Support vector machine algorithms provided the most accurate predictions with a root mean square error of cross validation of 29.0 ± 7.4 mg l<sup>-1</sup>and 3.9 ± 1.4 mg l<sup>-1</sup>for total and free VPA (mean ± SD), respectively. As a secondary analysis, we explored whether exhaled metabolites previously associated with side-effects and response to medication could be rendered by the off-line analysis method. We found that five features associated with side effects showed a CCC > 0.6, whereas none of the drug response-associated peaks reached this cut-off. We conclude that the clinically relevant free fraction of VPA can be predicted by this combination of off-line breath collection with rapid SESI-HRMS analysis. This opens new possibilities for breath based TDM in clinical settings.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":"17 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10306177","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 : 2023-09-07DOI: 10.1088/1752-7163/acf339
Amit Kumar, Deepak Joshi
The nasal dominance (ND) determination is crucial for nasal synchronized ventilator, optimum nasal drug delivery, identifying brain hemispheric dominance, nasal airway obstruction surgery, mindfulness breathing, and for possible markers of a conscious state. Given these wider applications of ND, it is interesting to understand the patterns of ND with varying temperature and respiration rates. In this paper, we propose a method which measures peak-to-peak temperature oscillations (difference between end-expiratory and end-inspiratory temperature) for the left and right nostrils during nasal breathing. These nostril-specific temperature oscillations are further used to calculate the nasal dominance index (NDI), nasal laterality ratio (NLR), inter-nostril correlation, and mean of peak-to-peak temperature oscillation for inspiratory and expiratory phase at (1) different ambient temperatures of 18 °C, 28 °C, and 38 °C and (2) at three different respiration rate of 6 bpm, 12 bpm, and 18 bpm. The peak-to-peak temperature (Tpp) oscillation range (averaged across participants;n= 8) for the left and right nostril were 3.80 ± 0.57 °C and 2.34 ± 0.61 °C, 2.03 ± 0.20 °C and 1.40 ± 0.26 °C, and 0.20 ± 0.02 °C and 0.29 ± 0.03 °C at the ambient temperature of 18 °C, 28 °C, and 38 °C respectively (averaged across participants and respiration rates). The NDI and NLR averaged across participants and three different respiration rates were 35.67 ± 5.53 and 2.03 ± 1.12; 8.36 ± 10.61 and 2.49 ± 3.69; and -25.04 ± 14.50 and 0.82 ± 0.54 at the ambient temperature of 18 °C, 28 °C, and 38 °C respectively. The Shapiro-Wilk test, and non-parametric Friedman test showed a significant effect of ambient temperature conditions on both NDI and NLR. No significant effect of respiration rate condition was observed on both NDI and NLR. The findings of the proposed study indicate the importance of ambient temperature while determining ND during the diagnosis of breathing disorders such as septum deviation, nasal polyps, nosebleeds, rhinitis, and nasal fractions, and in the intensive care unit for nasal synchronized ventilator.
{"title":"Effect of ambient temperature and respiration rate on nasal dominance: preliminary findings from a nostril-specific wearable.","authors":"Amit Kumar, Deepak Joshi","doi":"10.1088/1752-7163/acf339","DOIUrl":"https://doi.org/10.1088/1752-7163/acf339","url":null,"abstract":"<p><p>The nasal dominance (ND) determination is crucial for nasal synchronized ventilator, optimum nasal drug delivery, identifying brain hemispheric dominance, nasal airway obstruction surgery, mindfulness breathing, and for possible markers of a conscious state. Given these wider applications of ND, it is interesting to understand the patterns of ND with varying temperature and respiration rates. In this paper, we propose a method which measures peak-to-peak temperature oscillations (difference between end-expiratory and end-inspiratory temperature) for the left and right nostrils during nasal breathing. These nostril-specific temperature oscillations are further used to calculate the nasal dominance index (NDI), nasal laterality ratio (NLR), inter-nostril correlation, and mean of peak-to-peak temperature oscillation for inspiratory and expiratory phase at (1) different ambient temperatures of 18 °C, 28 °C, and 38 °C and (2) at three different respiration rate of 6 bpm, 12 bpm, and 18 bpm. The peak-to-peak temperature (<i>T</i><sub>pp</sub>) oscillation range (averaged across participants;<i>n</i>= 8) for the left and right nostril were 3.80 ± 0.57 °C and 2.34 ± 0.61 °C, 2.03 ± 0.20 °C and 1.40 ± 0.26 °C, and 0.20 ± 0.02 °C and 0.29 ± 0.03 °C at the ambient temperature of 18 °C, 28 °C, and 38 °C respectively (averaged across participants and respiration rates). The NDI and NLR averaged across participants and three different respiration rates were 35.67 ± 5.53 and 2.03 ± 1.12; 8.36 ± 10.61 and 2.49 ± 3.69; and -25.04 ± 14.50 and 0.82 ± 0.54 at the ambient temperature of 18 °C, 28 °C, and 38 °C respectively. The Shapiro-Wilk test, and non-parametric Friedman test showed a significant effect of ambient temperature conditions on both NDI and NLR. No significant effect of respiration rate condition was observed on both NDI and NLR. The findings of the proposed study indicate the importance of ambient temperature while determining ND during the diagnosis of breathing disorders such as septum deviation, nasal polyps, nosebleeds, rhinitis, and nasal fractions, and in the intensive care unit for nasal synchronized ventilator.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":"17 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230667","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 : 2023-09-07DOI: 10.1088/1752-7163/acf391
Conal Hayton, Waqar Ahmed, Peter Cunningham, Karen Piper-Hanley, Laurence Pearmain, Nazia Chaudhuri, Colm Leonard, John F Blaikley, Stephen J Fowler
Volatile organic compounds (VOCs) have shown promise as potential biomarkers in idiopathic pulmonary fibrosis. Measuring VOCs in the headspace ofin vitromodels of lung fibrosis may offer a method of determining the origin of those detected in exhaled breath. The aim of this study was to determine the VOCs associated with two lung cell lines (A549 and MRC-5 cells) and changes associated with stimulation of cells with the pro-fibrotic cytokine, transforming growth factor (TGF)-β1. A dynamic headspace sampling method was used to sample the headspace of A549 cells and MRC-5 cells. These were compared to media control samples and to each other to identify VOCs which discriminated between cell lines. Cells were then stimulated with the TGF-β1 and samples were compared between stimulated and unstimulated cells. Samples were analysed using thermal desorption-gas chromatography-mass spectrometry and supervised analysis was performed using sparse partial least squares-discriminant analysis (sPLS-DA). Supervised analysis revealed differential VOC profiles unique to each of the cell lines and from the media control samples. Significant changes in VOC profiles were induced by stimulation of cell lines with TGF-β1. In particular, several terpenoids (isopinocarveol, sativene and 3-carene) were increased in stimulated cells compared to unstimulated cells. VOC profiles differ between lung cell lines and alter in response to pro-fibrotic stimulation. Increased abundance of terpenoids in the headspace of stimulated cells may reflect TGF-β1 cell signalling activity and metabolic reprogramming. This may offer a potential biomarker target in exhaled breath in IPF.
{"title":"Changes in lung epithelial cell volatile metabolite profile induced by pro-fibrotic stimulation with TGF-<i>β</i>1.","authors":"Conal Hayton, Waqar Ahmed, Peter Cunningham, Karen Piper-Hanley, Laurence Pearmain, Nazia Chaudhuri, Colm Leonard, John F Blaikley, Stephen J Fowler","doi":"10.1088/1752-7163/acf391","DOIUrl":"https://doi.org/10.1088/1752-7163/acf391","url":null,"abstract":"<p><p>Volatile organic compounds (VOCs) have shown promise as potential biomarkers in idiopathic pulmonary fibrosis. Measuring VOCs in the headspace of<i>in vitro</i>models of lung fibrosis may offer a method of determining the origin of those detected in exhaled breath. The aim of this study was to determine the VOCs associated with two lung cell lines (A549 and MRC-5 cells) and changes associated with stimulation of cells with the pro-fibrotic cytokine, transforming growth factor (TGF)-<i>β</i>1. A dynamic headspace sampling method was used to sample the headspace of A549 cells and MRC-5 cells. These were compared to media control samples and to each other to identify VOCs which discriminated between cell lines. Cells were then stimulated with the TGF-<i>β</i>1 and samples were compared between stimulated and unstimulated cells. Samples were analysed using thermal desorption-gas chromatography-mass spectrometry and supervised analysis was performed using sparse partial least squares-discriminant analysis (sPLS-DA). Supervised analysis revealed differential VOC profiles unique to each of the cell lines and from the media control samples. Significant changes in VOC profiles were induced by stimulation of cell lines with TGF-<i>β</i>1. In particular, several terpenoids (isopinocarveol, sativene and 3-carene) were increased in stimulated cells compared to unstimulated cells. VOC profiles differ between lung cell lines and alter in response to pro-fibrotic stimulation. Increased abundance of terpenoids in the headspace of stimulated cells may reflect TGF-<i>β</i>1 cell signalling activity and metabolic reprogramming. This may offer a potential biomarker target in exhaled breath in IPF.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":"17 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10595305","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 : 2023-09-05DOI: 10.1088/1752-7163/acf066
Nynke Wijbenga, Marjolein M Muller, Rogier A S Hoek, Bas J Mathot, Leonard Seghers, Joachim G J V Aerts, Brenda C M de Winter, Daniel Bos, Olivier C Manintveld, Merel E Hellemons
In order to prevent long-term immunity-related complications after lung transplantation, close monitoring of immunosuppressant levels using therapeutic drug monitoring (TDM) is paramount. Novel electronic nose (eNose) technology may be a non-invasive alternative to the current invasive procedures for TDM. We investigated the diagnostic and categorization capacity of eNose breathprints for Tacrolimus trough blood plasma levels (TACtrough) in lung transplant recipients (LTRs). We performed eNose measurements in stable LTR attending the outpatient clinic. We evaluated (1) the correlation between eNose measurements and TACtrough, (2) the diagnostic capacity of eNose technology for TACtrough, and (3) the accuracy of eNose technology for categorization of TACtroughinto three clinically relevant categories (low: <7µg ml-1, medium: 7-10µg ml-1, and high: >10µg ml-1). A total of 186 measurements from 86 LTR were included. There was a weak but statistically significant correlation (r= 0.21,p= 0.004) between the eNose measurements and TACtrough. The root mean squared error of prediction for the diagnostic capacity was 3.186 in the training and 3.131 in the validation set. The accuracy of categorization ranged between 45%-63% for the training set and 52%-69% in the validation set. There is a weak correlation between eNose breathprints and TACtroughin LTR. However, the diagnostic as well as categorization capacity for TACtroughusing eNose breathprints is too inaccurate to be applicable in TDM.
{"title":"Diagnostic accuracy of eNose 'breathprints' for therapeutic drug monitoring of Tacrolimus trough levels in lung transplantation.","authors":"Nynke Wijbenga, Marjolein M Muller, Rogier A S Hoek, Bas J Mathot, Leonard Seghers, Joachim G J V Aerts, Brenda C M de Winter, Daniel Bos, Olivier C Manintveld, Merel E Hellemons","doi":"10.1088/1752-7163/acf066","DOIUrl":"https://doi.org/10.1088/1752-7163/acf066","url":null,"abstract":"<p><p>In order to prevent long-term immunity-related complications after lung transplantation, close monitoring of immunosuppressant levels using therapeutic drug monitoring (TDM) is paramount. Novel electronic nose (eNose) technology may be a non-invasive alternative to the current invasive procedures for TDM. We investigated the diagnostic and categorization capacity of eNose breathprints for Tacrolimus trough blood plasma levels (TAC<sub>trough</sub>) in lung transplant recipients (LTRs). We performed eNose measurements in stable LTR attending the outpatient clinic. We evaluated (1) the correlation between eNose measurements and TAC<sub>trough</sub>, (2) the diagnostic capacity of eNose technology for TAC<sub>trough</sub>, and (3) the accuracy of eNose technology for categorization of TAC<sub>trough</sub>into three clinically relevant categories (low: <7<i>µ</i>g ml<sup>-1</sup>, medium: 7-10<i>µ</i>g ml<sup>-1</sup>, and high: >10<i>µ</i>g ml<sup>-1</sup>). A total of 186 measurements from 86 LTR were included. There was a weak but statistically significant correlation (<i>r</i>= 0.21,<i>p</i>= 0.004) between the eNose measurements and TAC<sub>trough</sub>. The root mean squared error of prediction for the diagnostic capacity was 3.186 in the training and 3.131 in the validation set. The accuracy of categorization ranged between 45%-63% for the training set and 52%-69% in the validation set. There is a weak correlation between eNose breathprints and TAC<sub>trough</sub>in LTR. However, the diagnostic as well as categorization capacity for TAC<sub>trough</sub>using eNose breathprints is too inaccurate to be applicable in TDM.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":"17 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10531701","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 : 2023-09-04DOI: 10.1088/1752-7163/acf338
M Westhoff, M Keßler, J I Baumbach
Analyzing exhaled breath samples, especially using a highly sensitive method such as MCC/IMS (multi-capillary column/ion mobility spectrometry), may also detect analytes that are derived from exogenous production. In this regard, there is a discussion about the optimal interpretation of exhaled breath, either by considering volatile organic compounds (VOCs) only in exhaled breath or by additionally considering the composition of room air and calculating the alveolar gradients. However, there are no data on whether the composition and concentration of VOCs in room air are identical to those in truly inhaled air directly before analyzing the exhaled breath. The current study aimed to determine whether the VOCs in room air, which are usually used for the calculation of alveolar gradients, are identical to the VOCs in truly inhaled air. For the measurement of inhaled air and room air, two IMS, each coupled with an MCC that provided a pre-separation of the VOCs, were used in parallel. One device was used for sampling room air and the other for sampling inhaled air. Each device was coupled with a newly invented system that cleaned room air and provided a clean carrier gas, whereas formerly synthetic air had to be used as a carrier gas. In this pilot study, a healthy volunteer underwent three subsequent runs of sampling of inhaled air and simultaneous sampling and analysis of room air. Three of the selected 11 peaks (P4-unknown, P5-1-Butanol, and P9-Furan, 2-methyl-) had significantly higher intensities during inspiration than in room air, and four peaks (P1-1-Propanamine, N-(phenylmethylene), P2-2-Nonanone, P3-Benzene, 1,2,4-trimethyl-, and P11-Acetyl valeryl) had higher intensities in room air. Furthermore, four peaks (P6-Benzaldehyde, P7-Pentane, 2-methyl-, P8-Acetone, and P10-2-Propanamine) showed inconsistent differences in peak intensities between inhaled air and room air. To the best of our knowledge, this is the first study to compare simultaneous sampling of room air and inhaled air using MCC/IMS. The simultaneous measurement of inhaled air and room air showed that using room air for the calculation of alveolar gradients in breath analysis resulted in different alveolar gradient values than those obtained by measuring truly inhaled air.
{"title":"Alveolar gradients in breath analysis. A pilot study with comparison of room air and inhaled air by simultaneous measurements using ion mobility spectrometry.","authors":"M Westhoff, M Keßler, J I Baumbach","doi":"10.1088/1752-7163/acf338","DOIUrl":"https://doi.org/10.1088/1752-7163/acf338","url":null,"abstract":"<p><p>Analyzing exhaled breath samples, especially using a highly sensitive method such as MCC/IMS (multi-capillary column/ion mobility spectrometry), may also detect analytes that are derived from exogenous production. In this regard, there is a discussion about the optimal interpretation of exhaled breath, either by considering volatile organic compounds (VOCs) only in exhaled breath or by additionally considering the composition of room air and calculating the alveolar gradients. However, there are no data on whether the composition and concentration of VOCs in room air are identical to those in truly inhaled air directly before analyzing the exhaled breath. The current study aimed to determine whether the VOCs in room air, which are usually used for the calculation of alveolar gradients, are identical to the VOCs in truly inhaled air. For the measurement of inhaled air and room air, two IMS, each coupled with an MCC that provided a pre-separation of the VOCs, were used in parallel. One device was used for sampling room air and the other for sampling inhaled air. Each device was coupled with a newly invented system that cleaned room air and provided a clean carrier gas, whereas formerly synthetic air had to be used as a carrier gas. In this pilot study, a healthy volunteer underwent three subsequent runs of sampling of inhaled air and simultaneous sampling and analysis of room air. Three of the selected 11 peaks (P4-unknown, P5-1-Butanol, and P9-Furan, 2-methyl-) had significantly higher intensities during inspiration than in room air, and four peaks (P1-1-Propanamine, N-(phenylmethylene), P2-2-Nonanone, P3-Benzene, 1,2,4-trimethyl-, and P11-Acetyl valeryl) had higher intensities in room air. Furthermore, four peaks (P6-Benzaldehyde, P7-Pentane, 2-methyl-, P8-Acetone, and P10-2-Propanamine) showed inconsistent differences in peak intensities between inhaled air and room air. To the best of our knowledge, this is the first study to compare simultaneous sampling of room air and inhaled air using MCC/IMS. The simultaneous measurement of inhaled air and room air showed that using room air for the calculation of alveolar gradients in breath analysis resulted in different alveolar gradient values than those obtained by measuring truly inhaled air.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":"17 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10549128","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 : 2023-08-29DOI: 10.1088/1752-7163/acef4b
F M Vivaldi, S Reale, S Ghimenti, D Biagini, A Lenzi, T Lomonaco, F Di Francesco
Solid-phase sorption is widely used for the analysis of gaseous specimens as it allows at the same time to preconcentrate target analytes and store samples for relatively long periods. The addition of internal standards (ISs) in the analytical workflow can greatly reduce the variability of the analyses and improve the reliability of the protocols. In this work, we describe the development and testing of a portable system for the reliable production of gaseous mixture of8D-Toluene in a 1L Silonite canister as well as its reproducible loading into solid-phase sorbing tools as ISs. The portable system was tested using needle trap microextraction, solid-phase extraction, and thin-film microextraction techniques commonly employed for the analysis of gaseous samples. Even though our specific interest is in breath analysis, the system can also be used for the collection of any kind of gaseous specimen. A microcontroller allows the fine control of the sampling flow by a digital mass flow controller. Flow rate and sample volume could be set either through a rotary encoder mounted onto the control board or through a dedicated android app. The variability of the airflow is in the range 5-200 ml min-1and it is lower than 1%, whereas the variability of the IS (8D-Toluene) concentration dispensed over time by the loader measured by selected-ion flow-tube mass spectrometry (MS) is <3%. This combination resulted in intra- and inter-day precision of the amount loaded in the sorbent tools lower than 15%. No carry-over was detected in the loader after the delivery of the8D-Toluene measured by gas chromatography-MS. The8D-Toluene concentration in the canister was stable for up to three weeks at room temperature.
固相吸附法广泛用于气体样品的分析,因为它同时允许对目标分析物进行预浓缩,并将样品储存相对较长的时间。在分析工作流程中加入内部标准(ISs)可以大大减少分析的可变性,提高协议的可靠性。在这项工作中,我们描述了一种便携式系统的开发和测试,该系统用于在1L硅土罐中可靠地生产8d -甲苯的气体混合物,并将其可重复加载到固相吸附工具中作为ISs。便携式系统使用针阱微萃取、固相萃取和薄膜微萃取技术进行了测试,这些技术通常用于分析气体样品。尽管我们对呼气分析感兴趣,但该系统也可用于收集任何种类的气体样本。微控制器允许通过数字质量流量控制器对采样流量进行精细控制。流速和样本量可以通过安装在控制板上的旋转编编器或通过专用的android应用程序进行设置。气流的变异性在5-200 ml min-1范围内,低于1%,而通过选择离子流管质谱(MS)测量的装载机分配的is (8d -甲苯)浓度随时间的变异性是通过气相色谱-MS测量的8d -甲苯。在室温下,罐内的8d -甲苯浓度可稳定达三周。
{"title":"A low-cost internal standard loader for solid-phase sorbing tools.","authors":"F M Vivaldi, S Reale, S Ghimenti, D Biagini, A Lenzi, T Lomonaco, F Di Francesco","doi":"10.1088/1752-7163/acef4b","DOIUrl":"https://doi.org/10.1088/1752-7163/acef4b","url":null,"abstract":"<p><p>Solid-phase sorption is widely used for the analysis of gaseous specimens as it allows at the same time to preconcentrate target analytes and store samples for relatively long periods. The addition of internal standards (ISs) in the analytical workflow can greatly reduce the variability of the analyses and improve the reliability of the protocols. In this work, we describe the development and testing of a portable system for the reliable production of gaseous mixture of<sup>8</sup>D-Toluene in a 1L Silonite canister as well as its reproducible loading into solid-phase sorbing tools as ISs. The portable system was tested using needle trap microextraction, solid-phase extraction, and thin-film microextraction techniques commonly employed for the analysis of gaseous samples. Even though our specific interest is in breath analysis, the system can also be used for the collection of any kind of gaseous specimen. A microcontroller allows the fine control of the sampling flow by a digital mass flow controller. Flow rate and sample volume could be set either through a rotary encoder mounted onto the control board or through a dedicated android app. The variability of the airflow is in the range 5-200 ml min<sup>-1</sup>and it is lower than 1%, whereas the variability of the IS (<sup>8</sup>D-Toluene) concentration dispensed over time by the loader measured by selected-ion flow-tube mass spectrometry (MS) is <3%. This combination resulted in intra- and inter-day precision of the amount loaded in the sorbent tools lower than 15%. No carry-over was detected in the loader after the delivery of the<sup>8</sup>D-Toluene measured by gas chromatography-MS. The<sup>8</sup>D-Toluene concentration in the canister was stable for up to three weeks at room temperature.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":"17 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234492","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 : 2023-08-29DOI: 10.1088/1752-7163/acf1bf
Iris G van der Sar, Nynke van Jaarsveld, Imme A Spiekerman, Floor J Toxopeus, Quint L Langens, Marlies S Wijsenbeek, Justin Dauwels, Catharina C Moor
Electronic nose (eNose) technology is an emerging diagnostic application, using artificial intelligence to classify human breath patterns. These patterns can be used to diagnose medical conditions. Sarcoidosis is an often difficult to diagnose disease, as no standard procedure or conclusive test exists. An accurate diagnostic model based on eNose data could therefore be helpful in clinical decision-making. The aim of this paper is to evaluate the performance of various dimensionality reduction methods and classifiers in order to design an accurate diagnostic model for sarcoidosis. Various methods of dimensionality reduction and multiple hyperparameter optimised classifiers were tested and cross-validated on a dataset of patients with pulmonary sarcoidosis (n= 224) and other interstitial lung disease (n= 317). Best performing methods were selected to create a model to diagnose patients with sarcoidosis. Nested cross-validation was applied to calculate the overall diagnostic performance. A classification model with feature selection and random forest (RF) classifier showed the highest accuracy. The overall diagnostic performance resulted in an accuracy of 87.1% and area-under-the-curve of 91.2%. After comparing different dimensionality reduction methods and classifiers, a highly accurate model to diagnose a patient with sarcoidosis using eNose data was created. The RF classifier and feature selection showed the best performance. The presented systematic approach could also be applied to other eNose datasets to compare methods and select the optimal diagnostic model.
{"title":"Evaluation of different classification methods using electronic nose data to diagnose sarcoidosis.","authors":"Iris G van der Sar, Nynke van Jaarsveld, Imme A Spiekerman, Floor J Toxopeus, Quint L Langens, Marlies S Wijsenbeek, Justin Dauwels, Catharina C Moor","doi":"10.1088/1752-7163/acf1bf","DOIUrl":"10.1088/1752-7163/acf1bf","url":null,"abstract":"<p><p>Electronic nose (eNose) technology is an emerging diagnostic application, using artificial intelligence to classify human breath patterns. These patterns can be used to diagnose medical conditions. Sarcoidosis is an often difficult to diagnose disease, as no standard procedure or conclusive test exists. An accurate diagnostic model based on eNose data could therefore be helpful in clinical decision-making. The aim of this paper is to evaluate the performance of various dimensionality reduction methods and classifiers in order to design an accurate diagnostic model for sarcoidosis. Various methods of dimensionality reduction and multiple hyperparameter optimised classifiers were tested and cross-validated on a dataset of patients with pulmonary sarcoidosis (<i>n</i>= 224) and other interstitial lung disease (<i>n</i>= 317). Best performing methods were selected to create a model to diagnose patients with sarcoidosis. Nested cross-validation was applied to calculate the overall diagnostic performance. A classification model with feature selection and random forest (RF) classifier showed the highest accuracy. The overall diagnostic performance resulted in an accuracy of 87.1% and area-under-the-curve of 91.2%. After comparing different dimensionality reduction methods and classifiers, a highly accurate model to diagnose a patient with sarcoidosis using eNose data was created. The RF classifier and feature selection showed the best performance. The presented systematic approach could also be applied to other eNose datasets to compare methods and select the optimal diagnostic model.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":"17 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169433","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 : 2023-08-25DOI: 10.1088/1752-7163/acf065
Quan Zhang, Binyue Chen, Guohua Liu
Respiratory diseases are one of the leading causes of human death and exacerbate the global burden of non-communicable diseases. Finding a method to assist clinicians pre-diagnose these diseases is an urgent task. Existing artificial intelligence-based methods can improve the clinical diagnosis efficiency, but still face challenges. For example, the lack of interpretability, the problem of information redundancy or missing caused by only using static data, the difficulty of model to learn the interdependence between features, and the performance of model is limited by sparse datasets, etc. To alleviate these problems, we propose a novel RQPA-Net. It consists of Q&A diagnosis module (QAD) and pathological inference module (PI). The QAD is responsible for interacting with patients, adjusting inquiry strategies dynamically and collecting effective information for disease diagnosis. The designed multi-subspace network can alleviate the problem that classical method is difficult to understand the interdependence between features. The deep reinforcement learning designed also can alleviate the problem of classical methods lack of interpretability. The PI is responsible for reasoning potential pathological relationships between diseases or symptoms based on existing knowledge. Through integrating the advantages of deep learning and reinforcement learning techniques, PI can handle sparse datasets. Finally, for auxiliary diagnosis, the model achieves 0.9780 ± 0.0002 Recall, 0.9778 ± 0.0003 Acc, 0.9779 ± 0.0003 Precision and 0.9780 ± 0.0003 F1-score on the test set. In terms of assisting pathological analysis, compared with the end-to-end model, our model achieves higher comprehensive performance on different tasks and datasets with different degrees of sparsity. Even in sparse datasets, it can effectively infer potential associations between diseases or symptoms, and has higher potential clinical application. In this paper, we propose a novel network structure, which can not only assist doctors in diagnosing diseases, but also contribute to explore the potential disease mechanisms. It provides a new perspective for integrating AI technology and clinical practice.
{"title":"Artificial intelligence can dynamically adjust strategies for auxiliary diagnosing respiratory diseases and analyzing potential pathological relationships.","authors":"Quan Zhang, Binyue Chen, Guohua Liu","doi":"10.1088/1752-7163/acf065","DOIUrl":"https://doi.org/10.1088/1752-7163/acf065","url":null,"abstract":"<p><p>Respiratory diseases are one of the leading causes of human death and exacerbate the global burden of non-communicable diseases. Finding a method to assist clinicians pre-diagnose these diseases is an urgent task. Existing artificial intelligence-based methods can improve the clinical diagnosis efficiency, but still face challenges. For example, the lack of interpretability, the problem of information redundancy or missing caused by only using static data, the difficulty of model to learn the interdependence between features, and the performance of model is limited by sparse datasets, etc. To alleviate these problems, we propose a novel RQPA-Net. It consists of Q&A diagnosis module (QAD) and pathological inference module (PI). The QAD is responsible for interacting with patients, adjusting inquiry strategies dynamically and collecting effective information for disease diagnosis. The designed multi-subspace network can alleviate the problem that classical method is difficult to understand the interdependence between features. The deep reinforcement learning designed also can alleviate the problem of classical methods lack of interpretability. The PI is responsible for reasoning potential pathological relationships between diseases or symptoms based on existing knowledge. Through integrating the advantages of deep learning and reinforcement learning techniques, PI can handle sparse datasets. Finally, for auxiliary diagnosis, the model achieves 0.9780 ± 0.0002 Recall, 0.9778 ± 0.0003 Acc, 0.9779 ± 0.0003 Precision and 0.9780 ± 0.0003 F1-score on the test set. In terms of assisting pathological analysis, compared with the end-to-end model, our model achieves higher comprehensive performance on different tasks and datasets with different degrees of sparsity. Even in sparse datasets, it can effectively infer potential associations between diseases or symptoms, and has higher potential clinical application. In this paper, we propose a novel network structure, which can not only assist doctors in diagnosing diseases, but also contribute to explore the potential disease mechanisms. It provides a new perspective for integrating AI technology and clinical practice.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":"17 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10476469","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}