Fulfilling the Promise of Breathomics: Considerations for the Discovery and Validation of Exhaled Volatile Biomarkers.

The exhaled breath represents an ideal matrix for noninvasive biomarker discovery, and exhaled metabolomics have the potential to be clinically useful in the era of precision medicine. In this concise translational review, we specifically address volatile organic compounds in the breath, with a view toward fulfilling the promise of these as actionable biomarkers, in particular, for lung diseases. We review the literature paying attention to seminal work linked to key milestones in breath research; discuss potential applications for breath biomarkers across disease areas and healthcare systems, including the perspectives of industry; and outline critical aspects of study design that will need to be considered for any pivotal research going forward if breath analysis is to provide robust validated biomarkers that meet the requirements for future clinical implementation.

Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma.

Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker signature to predict sputum eosinophilia in asthma. VOCs emitted into the space above sputum samples (headspace) from patients with severe asthma ( = 36) were collected onto sorbent tubes and analyzed using thermal desorption gas chromatography-mass spectrometry (GC-MS).

The EBM+ movement.

In this paper, I provide an introduction for biostatisticians and others to some recent work in the philosophy of medicine. Firstly, I give an overview of some philosophical arguments that are thought to create problems for a prominent approach towards establishing causal claims in medicine, namely, the Evidence-Based Medicine (EBM) approach. Secondly, I provide an overview of further recent work in the philosophy of medicine, which argues that mechanistic studies can help to address these problems.

Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness.

Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements.

Association of gut-related metabolites with respiratory symptoms in COVID-19: A proof-of-concept study.

Gut-related metabolites have been linked with respiratory disease. The crosstalk between the gut and lungs suggests that gut health may be compromised in COVID-19. The aims of the present study were to analyze a panel of gut-related metabolites (acetyl-L-carnitine, betaine, choline, L-carnitine, trimethylamine, and trimethylamine N-oxide) in patients with COVID-19, matched with healthy individuals and patients with non-COVID-19 respiratory symptoms.

The variability of volatile organic compounds in the indoor air of clinical environments.

The development of clinical breath-analysis is confounded by the variability of background volatile organic compounds (VOCs). Reliable interpretation of clinical breath-analysis at individual, and cohort levels requires characterisation of clinical-VOC levels and exposures. Active-sampling with thermal-desorption/gas chromatography-mass spectrometry recorded and evaluated VOC concentrations in 245 samples of indoor air from three sites in a large National Health Service (NHS) provider trust in the UK over 27 months.

Systematic review with meta-analysis of diagnostic test accuracy for COVID-19 by mass spectrometry.

Background: The global COVID-19 pandemic has led to extensive development in many fields, including the diagnosis of COVID-19 infection by mass spectrometry. The aim of this systematic review and meta-analysis was to assess the accuracy of mass spectrometry diagnostic tests developed so far, across a wide range of biological matrices, and additionally to assess risks of bias and applicability in studies published to date.

Method: 23 retrospective observational cohort studies were included in the systematic review using the PRISMA-DTA framework, with a total of 2858 COVID-19 positive participants and 2544 controls.

A systematic review of the diagnostic accuracy of volatile organic compounds in airway diseases and their relation to markers of type-2 inflammation.

Background: Asthma and COPD continue to cause considerable diagnostic and treatment stratification challenges. Volatile organic compounds (VOCs) have been proposed as feasible diagnostic and monitoring biomarkers in airway diseases.

Aims: To 1) conduct a systematic review evaluating the diagnostic accuracy of VOCs in diagnosing airway diseases; 2) understand the relationship between reported VOCs and biomarkers of type-2 inflammation; 3) assess the standardisation of reporting according to STARD and TRIPOD criteria; 4) review current methods of breath sampling and analysis.

The peppermint breath test benchmark for PTR-MS and SIFT-MS.

A major challenge for breath research is the lack of standardization in sampling and analysis. To address this, a test that utilizes a standardized intervention and a defined study protocol has been proposed to explore disparities in breath research across different analytical platforms and to provide benchmark values for comparison. Specifically, theinvolves the targeted analysis in exhaled breath of volatile constituents of peppermint oil after ingestion of the encapsulated oil.

Diagnosis of COVID-19 by exhaled breath analysis using gas chromatography-mass spectrometry.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has claimed over two and a half million lives worldwide so far. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is perceived to be seasonally recurrent, and a rapid noninvasive biomarker to accurately diagnose patients early on in their disease course will be necessary to meet the operational demands for COVID-19 control in the coming years.

Objective: The aim of this study was to evaluate the role of exhaled breath volatile biomarkers in identifying patients with suspected or confirmed COVID-19 infection, based on their underlying PCR status and clinical probability.

Breaking bad news: A randomized controlled trial to test a novel interactive course for medical students using blended learning.

Objective: Breaking bad news (BBN) is challenging for physicians and patients and specific communication strategies aim to improve these situations. This study evaluates whether an E-learning assignment could improve medical students' accurate recognition of BBN communication techniques.

Methods: This randomized controlled trial was conducted at the University of Basel.

Changes to the sebum lipidome upon COVID-19 infection observed via rapid sampling from the skin.

Background: The COVID-19 pandemic has led to an unprecedented demand for testing - for diagnosis and prognosis - as well as for investigation into the impact of the disease on the host metabolism. Sebum sampling has the potential to support both needs by looking at what the virus does to us, rather than looking for the virus itself.

Methods: In this pilot study, sebum samples were collected from 67 hospitalised patients (30 COVID-19 positive and 37 COVID-19 negative) by gauze swab.

Breathomics for the clinician: the use of volatile organic compounds in respiratory diseases.

Exhaled breath analysis has the potential to provide valuable insight on the status of various metabolic pathways taking place in the lungs locally and other vital organs, via systemic circulation. For years, volatile organic compounds (VOCs) have been proposed as feasible alternative diagnostic and prognostic biomarkers for different respiratory pathologies.We reviewed the currently published literature on the discovery of exhaled breath VOCs and their utilisation in various respiratory diseasesKey barriers in the development of clinical breath tests include the lack of unified consensus for breath collection and analysis and the complexity of understanding the relationship between the exhaled VOCs and the underlying metabolic pathways.

LabPipe: an extensible bioinformatics toolkit to manage experimental data and metadata.

Background: Data handling in clinical bioinformatics is often inadequate. No freely available tools provide straightforward approaches for consistent, flexible metadata collection and linkage of related experimental data generated locally by vendor software.

Results: To address this problem, we created LabPipe, a flexible toolkit which is driven through a local client that runs alongside vendor software and connects to a light-weight server.

Use of the ReCIVA device in breath sampling of patients with acute breathlessness: a feasibility study.

Introduction: Investigating acute multifactorial undifferentiated breathlessness and understanding the driving inflammatory processes can be technically challenging in both adults and children. Being able to validate noninvasive methods such as breath analysis would be a huge clinical advance. The ReCIVA® device allows breath samples to be collected directly onto sorbent tubes at the bedside for analysis of exhaled volatile organic compounds (eVOCs).

Automating and Extending Comprehensive Two-Dimensional Gas Chromatography Data Processing by Interfacing Open-Source and Commercial Software.

Comprehensive two-dimensional gas chromatography (GC×GC) is a powerful analytical tool for both nontargeted and targeted analyses. However, there is a need for more integrated workflows for processing and managing the resultant high-complexity datasets. End-to-end workflows for processing GC×GC data are challenging and often require multiple tools or software to process a single dataset.

A benchmarking protocol for breath analysis: the peppermint experiment.

Sampling of volatile organic compounds (VOCs) has shown promise for detection of a range of diseases but results have proved hard to replicate due to a lack of standardization. In this work we introduce the 'Peppermint Initiative'. The initiative seeks to disseminate a standardized experiment that allows comparison of breath sampling and data analysis methods.

Bologna backstage - experiences from behind the scenes of the reforms of the Basel medical curriculum.

Based on a six-year degree in medical studies which was characterized by a series of lectures without an over-arching concept, Basel decided to embark on reforms in 1995. The first wave of reforms (1998-2003) produced a hybrid curriculum structure with PbL teaching units, organized according to organ systems, in years 1-4 of medical studies, which met the demand for "clinical content in the pre-clinical phase". A focus on General Practice medicine was achieved by implementing the "One to one tutorial" in the 3 and 4 year of studies.

Reinforced reasoning in medicine.

Some philosophers have argued that evidence of underlying mechanisms does not provide evidence for the effectiveness of a medical intervention. One such argument appeals to the unreliability of mechanistic reasoning. However, mechanistic reasoning is not the only way that evidence of mechanisms might provide evidence of effectiveness.