Short-term modification of breathprint by Elexacaftor/Tezacaftor/Ivacaftor in a paediatric cohort.

Background: The triple combination Elexacaftor/Tezacaftor/Ivacaftor (ETI) translates into major respiratory improvements in adults; yet current clinical endpoints may prove insufficiently sensitive in young children. We hypothesised that ETI rapidly modifies the lungs' metabolism, resulting in changes in breath composition.

Methods: Eleven children with CF were enrolled in a longitudinal pilot study at the paediatric Necker hospital.

Combination of real-time and hyphenated mass spectrometry for improved characterisation of exhaled breath biomarkers in clinical research.

Exhaled breath volatilomics is a powerful non-invasive tool for biomarker discovery in medical applications, but compound annotation is essential for pathophysiological insights and technology transfer. This study was aimed at investigating the interest of a hybrid approach combining real-time proton transfer reaction-time-of-flight mass spectrometry (PTR-TOF-MS) with comprehensive thermal desorption-two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (TD-GCxGC-TOF-MS) to enhance the analysis and characterization of VOCs in clinical research, using COVID-19 as a use case. VOC biomarker candidates were selected from clinical research using PTR-TOF-MS fingerprinting in patients with COVID-19 and matched to the Human Breathomic Database.

Drugs Targeting Cough Receptors: New Therapeutic Options in Refractory or Unexplained Chronic Cough.

Refractory chronic cough is a disabling disease with very limited therapeutic options. A better understanding of cough pathophysiology has led to the development of emerging drugs targeting cough receptors. Recent strides have illuminated novel therapeutic avenues, notably centred on modulating transient receptor potential (TRP) channels, purinergic receptors, and neurokinin receptors.

Therapeutic drug monitoring of corticosteroids/β-agonists in the hair of patients with asthma: an open-label feasibility study.

Although adherence to inhaled medication is critically important for treatment efficiency, around half of patients taking these drugs are non-adherent or make critical errors when using their delivery device. Segmental hair analysis might be a valuable tool for therapeutic monitoring because hair concentrations reflect exposure from month to month. The objective of the present proof-of-concept study was to establish the feasibility of segmental hair analysis of inhaled budesonide and formoterol in asthma patients.

The IL-4/13-induced production of M2 chemokines by human lung macrophages is enhanced by adenosine and PGE.

Background And Purpose: Lung macrophages (LMs) are critically involved in respiratory diseases. The primary objective of the present study was to determine whether or not an adenosine analog (NECA) and prostaglandin E (PGE) affected the interleukin (IL)-4- and IL-13-induced release of M2a chemokines (CCL13, CCL17, CCL18, and CCL22) by human LMs.

Experimental Approach: Primary macrophages isolated from resected human lungs were incubated with NECA, PGE, roflumilast, or vehicle and stimulated with IL-4 or IL-13 for 24 h.

A benchmark study of data normalisation methods for PTR-TOF-MS exhaled breath metabolomics.

Volatilomics is the branch of metabolomics dedicated to the analysis of volatile organic compounds in exhaled breath for medical diagnostic or therapeutic monitoring purposes. Real-time mass spectrometry (MS) technologies such as proton transfer reaction (PTR) MS are commonly used, and data normalisation is an important step to discard unwanted variation from non-biological sources, as batch effects and loss of sensitivity over time may be observed. As normalisation methods for real-time breath analysis have been poorly investigated, we aimed to benchmark known metabolomic data normalisation methods and apply them to PTR-MS data analysis.

Enhanced real-time mass spectrometry breath analysis for the diagnosis of COVID-19.

Background: Although rapid screening for and diagnosis of coronavirus disease 2019 (COVID-19) are still urgently needed, most current testing methods are long, costly or poorly specific. The objective of the present study was to determine whether or not artificial-intelligence-enhanced real-time mass spectrometry breath analysis is a reliable, safe, rapid means of screening ambulatory patients for COVID-19.

Methods: In two prospective, open, interventional studies in a single university hospital, we used real-time, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of exhaled breath from adults requiring screening for COVID-19.

Guidelines for the management of chronic cough in adults. Endorsed by the French speaking society of respiratory diseases (Société de Pneumologie de Langue Française, SPLF), the Société Française d'Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou (SFORL), the Société Française de Phoniatrie et de Laryngologie (SFPL), the Société Nationale Française de Gastro-entérologie (SNFGE).

Patients with chronic cough experience a high alteration of quality of life. Moreover, chronic cough is a complex entity with numerous etiologies and treatments. In order to help clinicians involved in the management of patients with chronic cough, guidelines on chronic cough have been established by a group of French experts.

[Guidelines for the management of chronic cough in adults].

Patients with chronic cough experience major alteration in their quality of life. Given its numerous etiologies and treatments, this disease is a complex entity. To help clinicians involved in patient management of patients, guidelines have been issued by a group of French experts.

Alternative routes for tranexamic acid treatment in obstetric bleeding (WOMAN-PharmacoTXA trial): a randomised trial and pharmacological study in caesarean section births.

Objective: To examine the safety, efficacy and pharmacology of intravenous (IV), intramuscular (IM) and oral tranexamic acid (TXA) use in pregnant women.

Design: Randomised, open-label trial.

Setting: Hospitals in Pakistan and Zambia.

Assessment of an e-nose performance for the detection of COVID-19 specific biomarkers.

Early, rapid and non-invasive diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is needed for the prevention and control of coronavirus disease 2019 (COVID-19). COVID-19 mainly affects the respiratory tract and lungs. Therefore, analysis of exhaled breath could be an alternative scalable method for reliable SARS-CoV-2 screening.

Volatile metabolites differentiate air-liquid interface cultures after infection with .

Early detection of lung infection is critical to clinical diagnosis, treatment, and monitoring. Measuring volatile organic compounds (VOCs) in exhaled breath has shown promise as a rapid and accurate method of evaluating disease metabolism and phenotype. However, further investigations of the role and function of VOCs in bacterial-host-stress response is required and this can only be realised through representative models.

Ruxolitinib inhibits cytokine production by human lung macrophages without impairing phagocytic ability.

The Janus kinase (JAK) 1/2 inhibitor ruxolitinib has been approved in an indication of myelofibrosis and is a candidate for the treatment of a number of inflammatory or autoimmune diseases. We assessed the effects of ruxolitinib on lipopolysaccharide (LPS)- and poly (I:C)-induced cytokine production by human lung macrophages (LMs) and on the LMs' phagocytic activity. Human LMs were isolated from patients operated on for lung carcinoma.

Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review.

Objective: To review available data on tranexamic acid (TXA) plasma concentration needed to inhibit fibrinolysis and the time to achieve this concentration when giving TXA by different routes in humans. To identify ongoing trials assessing alternatives to intravenous TXA administration.

Methods: We updated two previous systematic reviews by searching MEDLINE, EMBASE, OviSP, and ISI Web of Science from database inception to July 2021.

Biomedical detection dogs for the identification of SARS-CoV-2 infections from axillary sweat and breath samples.

A Polymerase Chain Reaction (PCR) test of a nasal swab is still the 'gold standard' for detecting a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, PCR testing could be usefully complemented by non-invasive, fast, reliable, cheap methods for detecting infected individuals in busy areas (e.g.

ptairMS: real-time processing and analysis of PTR-TOF-MS data for biomarker discovery in exhaled breath.

Motivation: Analysis of volatile organic compounds (VOCs) in exhaled breath by proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) is of increasing interest for real-time, non-invasive diagnosis, phenotyping and therapeutic drug monitoring in the clinics. However, there is currently a lack of methods and software tools for the processing of PTR-TOF-MS data from cohorts and suited for biomarker discovery studies.

Results: We developed a comprehensive suite of algorithms that process raw data from patient acquisitions and generate the table of feature intensities.

Clinical Validation of a Volumetric Absorptive Micro-Sampling Device for Pharmacokinetic Studies With Tranexamic Acid.

We assessed the accuracy of tranexamic acid (TXA) concentrations measured in capillary whole blood using volumetric absorptive micro-sampling (VAMS) devices. Paired venous and VAMS capillary blood samples were collected from 15 healthy volunteers participating in a pharmacokinetic study of alternative routes (oral, IM and IV) of administering TXA. To assess accuracy across a range of concentrations, blood was drawn at different times after TXA administration.

Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages.

Obesity is associated with an elevated risk of severe respiratory infections and inflammatory lung diseases. The objectives were to investigate 1) the production of adiponectin by human lung explants, 2) the expression of the adiponectin receptors AdipoR1 and AdipoR2 by human lung macrophages (LMs), and 3) the impact of recombinant human adiponectin and a small-molecule APN receptor agonist (AdipoRon) on LMs activation. Human parenchyma explants and LMs were isolated from patients operated for carcinoma.

WOMAN-PharmacoTXA trial: Study protocol for a randomised controlled trial to assess the pharmacokinetics and pharmacodynamics of intramuscular, intravenous and oral administration of tranexamic acid in women giving birth by caesarean section.

Intravenous tranexamic acid (TXA) within 3 hours of birth significantly reduces death due to bleeding in women with postpartum haemorrhage (PPH). Most PPH deaths occur in the first hours after giving birth and treatment delay decreases survival.  One barrier to rapid TXA treatment is the need for intravenous injection.

Physiologically based modelling of tranexamic acid pharmacokinetics following intravenous, intramuscular, sub-cutaneous and oral administration in healthy volunteers.

Background: Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post-partum haemorrhage. Treatment success is dependant on early intervention and rapid systemic exposure to TXA. The requirement for intravenous (IV) administration can in some situations limit accessibility to TXA therapy.

Population pharmacokinetics of ropivacaine used for local infiltration anaesthesia during primary total unilateral and simultaneous bilateral knee arthroplasty.

Background: Ropivacaine is commonly used in local infiltration anaesthesia (LIA) as pain management after total knee arthroplasty (TKA). Although considered safe, no studies evaluated the pharmacokinetics of high-dose ropivacaine infiltration in simultaneous bilateral TKA.

Methods: We studied 13 patients undergoing unilateral and 15 undergoing bilateral TKA.

High-sensitivity quantification of acetylcholine and choline in human cerebrospinal fluid with a validated LC-MS/MS method.

Acetylcholine is the neurotransmitter of the parasympathetic nervous system, synthesized from choline and involved in several neurodegenerative diseases. Exploration of cholinergic neurotransmission in the human central nervous system is limited by the lack of a sensitive and specific method for the determination of acetylcholine and choline expression. We developed an hydrophilic interaction liquid chromatography - mass spectrometry method for the quantification of both molecules in human cerebrospinal fluid samples.

Clinical Relevance of the Anti-inflammatory Effects of Roflumilast on Human Bronchus: Potentiation by a Long-Acting Beta-2-Agonist.

Roflumilast is an option for treating patients with severe COPD and frequent exacerbations despite optimal therapy with inhaled drugs. The present study focused on whether the phosphodiesterase (PDE) 4 inhibitor roflumilast and its active metabolite roflumilast N-oxide affect the release of tumor necrosis factor (TNF)-α and chemokines by lipopolysaccharide (LPS)-stimulated human bronchial explants. We also investigated the interactions between roflumilast, roflumilast N-oxide and the β-agonist formoterol with regard to cytokine release by the bronchial preparations.

Metabolomics of exhaled breath in critically ill COVID-19 patients: A pilot study.

Background: Early diagnosis of coronavirus disease 2019 (COVID-19) is of the utmost importance but remains challenging. The objective of the current study was to characterize exhaled breath from mechanically ventilated adults with COVID-19.

Methods: In this prospective observational study, we used real-time, online, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of expired air from adults undergoing invasive mechanical ventilation in the intensive care unit due to severe COVID-19 or non-COVID-19 acute respiratory distress syndrome (ARDS).