ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases

The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients’ perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2–3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data.The document facilitates standardisation of conducting, reporting and interpreting cardiopulmonary exercise tests in chronic lung diseases for comparison of reference data, multi-centre studies and assessment of interventional efficacy. http://bit.ly/31SXeB

Determination of the Frequency Response of an End Tidal CO2 Analyser

In a health care environment, mechanical ventilation is used to support patients during acute illness and surgery. Mechanical ventilation is the process by which the patient’s respiratory function is artificially supported using a respirator. During mechanical ventilation, it is necessary to ensure the adequacy of ventilation. The patient is thus monitored for several ventilatory parameters. The end-tidal CO2 (EtCO2) is one of the primary monitoring parameters. EtCO2 is the partial pressure or maximal concentration of carbon dioxide (CO2) at the end of an exhaled breath, which is expressed as a percentage of CO2 or mmHg . Capnography is the technique that graphs out expired CO2 as a function of time and measures EtCO2. The measuring device is called a capnometer and the waveform displayed by the capnograph is called capnogram

Methods and protocols for incremental exercise testing in tetraplegia, using arm-crank ergometry assisted by Functional Electrical Stimulation

Cervical spinal cord injury (SCI) leads to tetraplegia, with paralysis and loss of sensation in the upper and lower limbs. The associated sedentary lifestyle results in an increased risk of cardiovascular disease. To address this, we require the design of exercise modalities aimed specifically at tetraplegia and methods to assess their efficacy. This paper describes methods for arm-crank ergometry (ACE) assisted by Functional Electrical Stimulation (FES) applied to the biceps and triceps. The instrumented ergometer enables work-rate control during exercise, implemented here for incremental exercise testing during FES-ACE. Detailed protocols for the tests are given. Experimental data collected during exercise tests with tetraplegic volunteers are provided to illustrate the feasibility of the proposed approach to testing and data analysis. Incremental tests enabled calculation of peak power output and peak oxygen uptake. We propose that the high-precision exercise testing protocols described here are appropriate to assess the efficacy of the novel exercise modality, FES-ACE, in tetraplegia

A holistic approach to host-pathogen interactions : Detecting the large to unravel the small

Sepsis is one of the leading causes of mortality and morbidity in the world, and is an overreaction by the immune system due to pathogen invasion of the bloodstream. The interactions, particularly the protein interactions, between the host and pathogen are fundamental for the outcome of the disease. However, some of the protein interactions are unknown and those that are known have been studied as single entities. This thesis focuses on expanding the knowledge of these interactions. In addition, the thesis emphasises the analysis of every interaction at the same time. The identification and quantification of the whole network of interactions is central to determine the impact of single proteins, since the interactions can be co-dependent. The proteins of the human immune system are of particular interest since the pathogens have to avoid the immune system in order to survive in the host. Using state of the art techniques, the human plasma interaction proteome for several pathogens were determined and several novel interactions were discovered. For the gram-positive bacterium Streptococcus pyogenes, the interaction proteome was determined with higher accuracy than ever before. In conclusion, when focusing on the whole interaction pattern the specific details can be explained. The wider understanding of the field of host-pathogen interactions that is established with this thesis aids in future development of diagnostics and therapeutics in pathogen related diseases

Novel methods for the rapid and selective analysis of biological samples using hyphenated ion mobility-mass spectrometry with ambient ionization

The increased use of mass spectrometry in the clinical setting has led to a demand for high sample throughput. Developments such as ultra high performance liquid chromatography and the ambient ionization techniques enable high sample throughput by reducing chromatographic run times or by removing the requirement for sample preparation and fractionation prior to analysis. This thesis assesses the reproducibility and robustness of these high throughput techniques for the analysis of clinical and pharmaceutical samples by ion mobility-mass spectrometry. The rapid quantitative analysis of the urinary biomarkers of chronic obstructive pulmonary disease, desmosine and isodesmosine has been performed by ultra high performance liquid chromatography combined with ion mobility-mass spectrometry. The determination of health status based on the free unbound fraction rather than the total bound and unbound desmosine and isodesmosine, significantly reduces the time taken in sample preparation. The potential for direct analysis of the urinary metabolites from undeveloped TLC plates using a solvent extraction surface sample probe is demonstrated. The use of a solvent gradient for the extraction separates urinary metabolites from salts and other matrix components and allows fractionation of the sample as a result of differential retention on the undeveloped RP-TLC plate. This separation, combined with ion mobility-mass spectrometry provides a rapid ambient ionization method for urinary profiling. The combination of a thermal desorption probe with extractive electrospray ionization has been applied to the direct detection of a known genotoxic impurity from a surrogate active pharmaceutical ingredient. The volatility of the impurity compared to the matrix, allowed selective thermal desorption of the analyte, which was ionized by extractive electrospray and detected by mass spectrometry. The use of a rapid on-probe derivatisation reaction, combined with thermal desorption is demonstrated for the direct determination of urinary creatinine. The aqueous acylation of creatinine significantly increases the volatility of the analyte enabling separation from the urine matrix and analysis by thermal desorption extractive electrospray combined with ion mobility-mass spectrometry

ARTP statement on cardiopulmonary exercise testing 2021.

Cardiopulmonary exercise testing (CPET) has become an invaluable tool in healthcare, improving the diagnosis of disease and the quality, efficacy, assessment and safety of treatment across a range of pathologies. CPET's superior ability to measure the global exercise response of the respiratory, cardiovascular and skeletal muscle systems simultaneously in a time and cost-efficient manner has led to the application of CPET in a range of settings from diagnosis of disease to preoperative assessment. The Association for Respiratory Technology and Physiology Statement on Cardiopulmonary Exercise Testing 2021 provides the practitioner and scientist with an outstanding resource to support and enhance practice, from equipment to testing to leadership, helping them deliver a quality assured service for the benefit of all patient groups

To metabolomics and beyond: a technological portfolio to investigate cancer metabolism

Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression, metastasis and resistance to therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosynthetic and redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field has seen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell or a tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinical applications in oncology. Metabolomics and fluxomics, are key technological approaches that mainly revolutionized the field enabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, the upgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellular resolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent of functional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and novel therapeutic targets that in concert with other technologies allow patient stratification and identification of new treatment regimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emerging technologies, emphasizing advantages, disadvantages and applications with the potential of leading the development of innovative anti-cancer therapies