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Clinical Chemistry Dec 2021Starkly highlighted by the current COVID-19 pandemic, infectious diseases continue to have an outsized impact on human health worldwide. Diagnostic testing for infection... (Review)
Review
BACKGROUND
Starkly highlighted by the current COVID-19 pandemic, infectious diseases continue to have an outsized impact on human health worldwide. Diagnostic testing for infection can be challenging due to resource limitations, time constraints, or shortcomings in the accuracy of existing diagnostics. Rapid, simple diagnostics are highly desirable. There is increasing interest in the development of diagnostics that use exhaled breath analysis as a convenient and safe diagnostic method, as breath sampling is noninvasive, secure, and easy to perform. Volatile organic compounds (VOCs) present in exhaled breath reflect the fingerprint of the underlying metabolic and biophysical processes during disease.
CONTENT
In this review, we overview the major biomarkers present in exhaled breath in infectious diseases. We outline the promising recent advances in breath-based diagnosis of respiratory infections, including those caused by influenza virus, SARS-CoV-2, Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Aspergillus fumigatus. In addition, we review the current landscape of diagnosis of 2 other globally important infections: Helicobacter pylori gastrointestinal infection and malaria.
SUMMARY
Characteristic and reproducible breath VOCs are associated with several infectious diseases, suggesting breath analysis as a promising strategy for diagnostic development. Ongoing challenges include poor standardization of breath collection and analysis and lack of validation studies. Further research is required to expand the applicability of breath analysis to clinical settings.
Topics: Breath Tests; Communicable Diseases; Exhalation; Humans; Volatile Organic Compounds
PubMed: 34969107
DOI: 10.1093/clinchem/hvab218 -
Current Opinion in Allergy and Clinical... Apr 2018Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying... (Review)
Review
PURPOSE OF REVIEW
Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying children at risk of an asthma attack affords the opportunity to prevent attacks and improve outcomes.
RECENT FINDINGS
Clinical features, patient behaviours and characteristics, physiological factors, environmental data and biomarkers are all associated with asthma attacks and can be used in asthma exacerbation prediction models. Recent studies have better characterized children at risk of an attack: history of a severe exacerbation in the previous 12 months, poor adherence and current poor control are important features which should alert healthcare professionals to the need for remedial action. There is increasing interest in the use of biomarkers. A number of novel biomarkers, including patterns of volatile organic compounds in exhaled breath, show promise. Biomarkers are likely to be of greatest utility if measured frequently and combined with other measures. To date, most prediction models are based on epidemiological data and population-based risk. The use of digital technology affords the opportunity to collect large amounts of real-time data, including clinical and physiological measurements and combine these with environmental data to develop personal risk scores. These developments need to be matched by changes in clinical guidelines away from a focus on current asthma control and stepwise escalation in drug therapy towards inclusion of personal risk scores and tailored management strategies including nonpharmacological approaches.
SUMMARY
There have been significant steps towards personalized prediction models of asthma attacks. The utility of such models needs to be tested in the ability not only to predict attacks but also to reduce them.
Topics: Anti-Asthmatic Agents; Asthma; Biomarkers; Breath Tests; Child; Disease Progression; Environmental Exposure; Exhalation; Humans; Models, Biological; Nitric Oxide; Predictive Value of Tests; Prognosis; Risk Assessment; Symptom Flare Up
PubMed: 29406359
DOI: 10.1097/ACI.0000000000000428 -
Journal of Clinical Sleep Medicine :... Mar 2016Lung mechanics in the overlap of COPD and sleep apnea impact the severity of sleep apnea. Specifically, increased lung compliance with hyperinflation protects against...
STUDY OBJECTIVES
Lung mechanics in the overlap of COPD and sleep apnea impact the severity of sleep apnea. Specifically, increased lung compliance with hyperinflation protects against sleep apnea, whereas increased airway resistance worsens sleep apnea. We sought to assess whether the expiratory time constant, which reflects lung mechanics, is associated with sleep apnea severity in such patients.
METHODS
Polysomnographies in 34 subjects with the overlap syndrome were reviewed. Three time constants were measured for each of up to 5 stages (wake, NREM stages, and REM). The time constants were derived by fitting time and pressure coordinates on the expiratory portion of a nasal pressure signal along an exponentially decaying equation, and solving for the time constant. Demographics, morphometrics, wake end-tidal CO2, right diaphragmatic arc on a chest radiograph, and the apnea-hypopnea index (AHI) were recorded.
RESULTS
The time constant was not associated with age, gender, body mass index, right diaphragmatic arc, or wake end-tidal CO2, and was not significantly different between sleep stages. A mean time constant (TC) was therefore obtained. Subjects with a TC > 0.5 seconds had a greater AHI than those with a TC ≤ 0.5 seconds (median AHI 58 vs. 18, respectively, p = 0.003; Odds ratio of severe sleep apnea 10.6, 95% CI 3.9-51.1, p = 0.005).
CONCLUSIONS
A larger time constant in the overlap syndrome is associated with increased odds of severe sleep apnea, suggesting a greater importance of airway resistance relative to lung compliance in sleep apnea causation in these subjects.
Topics: Aged; Airway Resistance; Exhalation; Female; Humans; Male; Polysomnography; Pulmonary Disease, Chronic Obstructive; Respiration; Respiratory Function Tests; Severity of Illness Index; Sleep Apnea Syndromes; Sleep Stages; Time
PubMed: 26414979
DOI: 10.5664/jcsm.5576 -
Clinical Chemistry and Laboratory... Jul 2013Since the late 1990s, a surge in interest in the analysis of exhaled breath condensate (EBC) resulted in the American Thoracic Society and European Respiratory Society... (Review)
Review
Since the late 1990s, a surge in interest in the analysis of exhaled breath condensate (EBC) resulted in the American Thoracic Society and European Respiratory Society (ATS/ERS) organising a Task Force in 2001 to develop guidelines on EBC collection and measurement of biomarkers. This Task Force published their guidelines in 2005 based on literature and expert opinions at that time, and multiple shortcomings and knowledge deficits were also identified. The clinical application of EBC collection and its biomarkers are currently still limited by several of these knowledge gaps, hence further guidelines for standardisation are required to ensure external validity. Using related articles produced since the publication of the ATS/ERS Task Force report, this paper attempts to provide a comprehensive update to the original guideline and review the methodological shortcomings identified. This review can hopefully serve as a yardstick for future studies involving this emerging clinical tool.
Topics: Age Factors; Biological Assay; Biomarkers; Breath Tests; Cytokines; Eicosanoids; Exhalation; Humans; Hydrogen Peroxide; Practice Guidelines as Topic; Reproducibility of Results; Sensitivity and Specificity; Sex Factors; Specimen Handling
PubMed: 23420285
DOI: 10.1515/cclm-2012-0593 -
BMC Pulmonary Medicine Nov 2019The expiratory time constant (RC), which is defined as the product of airway resistance and lung compliance, enable us to assess the mechanical properties of the...
BACKGROUND
The expiratory time constant (RC), which is defined as the product of airway resistance and lung compliance, enable us to assess the mechanical properties of the respiratory system in mechanically ventilated patients. Although RC could also be applied to spontaneously breathing patients, little is known about RC calculated from the maximal expiratory flow-volume (MEFV) curve. The aim of our study was to determine the reference value for RC, as well as to investigate the association between RC and other respiratory function parameters, including the forced expiratory volume in 1 s (FEV)/ forced vital capacity (FVC) ratio, maximal mid-expiratory flow rate (MMF), maximal expiratory flow at 50 and 25% of FVC (MEF and MEF, respectively), ratio of MEF to MEF (MEF/MEF).
METHODS
Spirometric parameters were extracted from the records of patients aged 15 years or older who underwent pulmonary function testing as a routine preoperative examination before non-cardiac surgery at the University of Tokyo Hospital. RC was calculated in each patient from the slope of the descending limb of the MEFV curve using two points corresponding to MEF and MEF. Airway obstruction was defined as an FEV/FVC and FEV below the statistically lower limit of normal.
RESULTS
We retrospectively analyzed 777 spirometry records, and 62 patients were deemed to have airway obstruction according to Japanese spirometric reference values. The cut-off value for RC was 0.601 s with an area under the receiver operating characteristic curve of 0.934 (95% confidence interval = 0.898-0.970). RC was strongly associated with FEV/FVC, and was moderately associated with MMF and MEF. However, RC was less associated with MEF and MEF/MEF.
CONCLUSIONS
Our findings suggest that an RC of longer than approximately 0.6 s can be linked to the presence of airway obstruction. Application of the concept of RC to spontaneously breathing subjects was feasible, using our simple calculation method.
Topics: Adolescent; Airway Obstruction; Exhalation; Feasibility Studies; Female; Humans; Lung; Male; Maximal Expiratory Flow-Volume Curves; Predictive Value of Tests; Preoperative Period; ROC Curve; Reference Values; Retrospective Studies; Spirometry; Surgical Procedures, Operative
PubMed: 31711456
DOI: 10.1186/s12890-019-0976-6 -
Journal of Cystic Fibrosis : Official... Jan 2022Pseudomonas aeruginosa (PA) is an important respiratory pathogen for cystic fibrosis (CF) patients. Routine microbiology surveillance is time-consuming, and is best... (Review)
Review
BACKGROUND
Pseudomonas aeruginosa (PA) is an important respiratory pathogen for cystic fibrosis (CF) patients. Routine microbiology surveillance is time-consuming, and is best performed on expectorated sputum. As alternative, volatile organic compounds (VOCs) may be indicative of PA colonisation. In this study, we aimed to identify VOCs associated with PA in literature and perform targeted exhaled breath analysis to recognize PA positive CF patients non-invasively.
METHODS
This study consisted of 1) a literature review to select VOCs of interest, and 2) a cross-sectional CF study. Definitions used: A) PA positive, PA culture at visit/chronically; B) PA free, no PA culture in ≥12 months. Exhaled VOCs were identified via quadrupole MS. The primary endpoint was the area under the receiver operating characteristics curve (AUROCC) of individual VOCs as well as combined VOCs against PA culture.
RESULTS
241 VOCs were identified in literature, of which 56 were further evaluated, and 13 could be detected in exhaled breath in our cohort. Exhaled breath of 25 pediatric and 28 adult CF patients, PA positive (n=16) and free (n=28) was available. 3/13 VOCs were significantly (p<0.05) different between PA groups in children; none were in adults. Notably, a composite model based on 5 or 1 VOC(s) showed an AUROCC of 0.86 (CI 0.71-1.0) and 0.87 (CI 0.72-1.0) for adults and children, respectively.
CONCLUSIONS
Targeted VOC analysis appears to discriminate children and adults with and without PA positive cultures with clinically acceptable sensitivity values.
Topics: Adolescent; Adult; Breath Tests; Cross-Sectional Studies; Cystic Fibrosis; Exhalation; Female; Humans; Longitudinal Studies; Male; Pseudomonas Infections; Pseudomonas aeruginosa; Volatile Organic Compounds; Young Adult
PubMed: 34016557
DOI: 10.1016/j.jcf.2021.04.015 -
Journal of Pharmaceutical and... Oct 2021The advantages that on-line breath analysis has shown in different fields have already made it stand as an interesting tool for pharmacokinetic studies. This review... (Review)
Review
The advantages that on-line breath analysis has shown in different fields have already made it stand as an interesting tool for pharmacokinetic studies. This review summarizes recent progress in the field, diving into the different analytical methods and the different advantages and hurdles encountered. We conclude that there is a wealth of limitations in the application of this technique, and key aspects like standardization are still outstanding. Nevertheless, this is an experimental field that has not yet been fully explored; and the advantages it offers for animal welfare, decrease in the amount of drug needed in experimental studies, and complementary insights to current pharmacological studies, warrant further exploration. Further studies are needed to overcome current limitations and incorporate this technique into the toolbox of pharmacological studies, both at an industrial and academic level.
Topics: Animals; Breath Tests; Exhalation; Reference Standards
PubMed: 34403867
DOI: 10.1016/j.jpba.2021.114311 -
Experimental Physiology Oct 2015What is the central question of this study? Does the induction of a model of lung injury affect the expiratory time constant (τE) in terms of either total duration or... (Comparative Study)
Comparative Study
What is the central question of this study? Does the induction of a model of lung injury affect the expiratory time constant (τE) in terms of either total duration or morphology? Does ventilation with gases of different densities alter the duration or morphology of τE either before or after injury? What is the main finding and its importance? The use of sulfur hexafluoride in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both nitrogen and helium mixtures. Sulfur hexafluoride mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with nitrogen and helium mixtures. Acute lung injury is characterized by regional heterogeneity of lung resistance and elastance that may lead to regional heterogeneity of expiratory time constants (τE). We hypothesized that increasing airflow resistance by using inhaled sulfur hexafluoride (SF6) would lengthen time constants and decrease their heterogeneity in an experimental model of lung injury when compared with nitrogen or helium mixtures. To overcome the limitations of a single-compartment model, we employed a multisegment model of expiratory gas flow. An experimental model of lung injury was created using intratracheal injection of sodium polyacrylate in anaesthetized and mechanically ventilated female Yorkshire-cross pigs (n = 7). The animals were ventilated with 50% O2 and the remaining 50% as nitrogen (N2), helium (He) or sulfur hexafluoride (SF6). Values for τE decreased with injury and were more variable after injury than before (P < 0.001). Values for τE increased throughout expiration both before and after injury, and the rate of increase in τE was lessened by SF6 (P < 0.001 when compared with N2 both before and after injury). Altering the inhaled gas density did not affect indices of oxygenation, dead space or shunt. The use of SF6 in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both N2 and He mixtures. Importantly, SF6 mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with N2 and He mixtures.
Topics: Acrylic Resins; Acute Lung Injury; Administration, Inhalation; Animals; Disease Models, Animal; Exhalation; Female; Gases; Helium; Lung; Models, Biological; Nitrogen; Respiration, Artificial; Specific Gravity; Sulfur Hexafluoride; Sus scrofa; Time Factors
PubMed: 26289254
DOI: 10.1113/EP085205 -
Sensors (Basel, Switzerland) Jan 2019A single exhale breathalyzer comprises a gas sensor that satisfies the following stringent conditions: high sensitivity to the target gas, high selectivity, stable...
A single exhale breathalyzer comprises a gas sensor that satisfies the following stringent conditions: high sensitivity to the target gas, high selectivity, stable response over extended period of time and fast response. Breathalyzer implementation includes a front-end circuit matching the sensitivity of the sensor that provides the readout of the sensor signal. We present here the characterization study of the response stability and response time of a selective Nitric Oxide (NO) sensor using designed data acquisition system that also serves as a foundation for the design of wireless handheld prototype. The experimental results with the described sensor and data acquisition system demonstrate stable response to NO concentration of 200 ppb over the period of two weeks. The experiments with different injection and retraction times of the sensor exposure to constant NO concentration show a fast response time of the sensor (on the order of 15 s) and the adequate recovery time (on the order of 3 min) demonstrating suitability for the single exhale breathalyzer.
Topics: Biomarkers; Biosensing Techniques; Breath Tests; Exhalation; Humans; Nitric Oxide; Wireless Technology
PubMed: 30641922
DOI: 10.3390/s19020270 -
Critical Care (London, England) Feb 2013We hypothesized the expiratory time constant (ƬE) may be used to provide real time determinations of inspiratory plateau pressure (Pplt), respiratory system compliance...
INTRODUCTION
We hypothesized the expiratory time constant (ƬE) may be used to provide real time determinations of inspiratory plateau pressure (Pplt), respiratory system compliance (Crs), and total resistance (respiratory system resistance plus series resistance of endotracheal tube) (Rtot) of patients with respiratory failure using various modes of ventilatory support.
METHODS
Adults (n = 92) with acute respiratory failure were categorized into four groups depending on the mode of ventilatory support ordered by attending physicians, i.e., volume controlled-continuous mandatory ventilation (VC-CMV), volume controlled-synchronized intermittent mandatory ventilation (VC-SIMV), volume control plus (VC+), and pressure support ventilation (PSV). Positive end expiratory pressure as ordered was combined with all aforementioned modes. Pplt, determined by the traditional end inspiratory pause (EIP) method, was combined in equations to determine Crs and Rtot. Following that, the ƬE method was employed, ƬE was estimated from point-by-point measurements of exhaled tidal volume and flow rate, it was then combined in equations to determine Pplt, Crs, and Rtot. Both methods were compared using regression analysis.
RESULTS
ƬE, ranging from mean values of 0.54 sec to 0.66 sec, was not significantly different among ventilatory modes. The ƬE method was an excellent predictor of Pplt, Crs, and Rtot for various ventilatory modes; r2 values for the relationships of ƬE and EIP methods ranged from 0.94 to 0.99 for Pplt, 0.90 to 0.99 for Crs, and 0.88 to 0.94 for Rtot (P <0.001). Bias and precision values were negligible.
CONCLUSIONS
We found the ƬE method was just as good as the EIP method for determining Pplt, Crs, and Rtot for various modes of ventilatory support for patients with acute respiratory failure. It is unclear if the ƬE method can be generalized to patients with chronic obstructive lung disease. ƬE is determined during passive deflation of the lungs without the need for changing the ventilatory mode and disrupting a patient's breathing. The ƬE method obviates the need to apply an EIP, allows for continuous and automatic surveillance of inspiratory Pplt so it can be maintained ≤ 30 cm H₂O for lung protection and patient safety, and permits real time assessments of pulmonary mechanics.
Topics: Adult; Aged; Exhalation; Female; Humans; Lung Compliance; Male; Middle Aged; Positive-Pressure Respiration; Respiration, Artificial; Respiratory Distress Syndrome; Tidal Volume; Time Factors
PubMed: 23384402
DOI: 10.1186/cc12500