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.

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.

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.

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.

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.

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.

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).

Clinical relevance of the relaxant effects of roflumilast on human bronchus: potentiation by a long-acting beta-2-agonist.

Roflumilast is an oral, add-on option for treating patients with severe COPD and frequent exacerbations despite optimal therapy with inhaled drugs. The present study focused on whether this phosphodiesterase 4 inhibitor and its active metabolite roflumilast N-oxide affect the tone of human bronchial rings. We also investigated the interactions between roflumilast, roflumilast N-oxide and the long-acting β -agonist formoterol with regard to the relaxation of isolated human bronchial rings at basal tone or pre-contracted with histamine.

Chloroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants.

On human lung parenchymal explants, chloroquine concentration clinically achievable in the lung (100 µM) inhibited the lipopolysaccharide-induced release of TNF-ɑ (by 76%), IL-6 (by 68%), CCL2 (by 72%), and CCL3 (by 67%). Besides its antiviral activity, chloroquine might also mitigate the cytokine storm associated with severe pneumonia caused by coronaviruses.

Contrasting Effects of Adipokines on the Cytokine Production by Primary Human Bronchial Epithelial Cells: Inhibitory Effects of Adiponectin.

Background: Obesity is associated with an elevated risk of respiratory infections and inflammatory lung diseases. The objective was to investigate (i) the effects of adipokines (adiponectin (APN), leptin, chemerin, and visfatin) on the production of cytokines by unstimulated and poly(I:C)- and TNF-α-activated human primary bronchial epithelial cells (hBECs), (ii) the cells' expression of the APN receptors (AdipoR1 and AdipoR2), and (iii) the cells' production of APN.

Methods: The hBECs were isolated from patients undergoing surgery for lung carcinoma.

Bitter Taste Receptors (TAS2Rs) in Human Lung Macrophages: Receptor Expression and Inhibitory Effects of TAS2R Agonists.

Background: Bitter-taste receptors (TAS2Rs) are involved in airway relaxation but are also expressed in human blood leukocytes. We studied TAS2R expression and the effects of TAS2R agonists on the lipopolysaccharide (LPS)-induced cytokine release in human lung macrophages (LMs).

Methods: Lung macrophages were isolated from patients undergoing surgery for carcinoma.

A split-range acquisition method for the non-targeted metabolomic profiling of human plasma with hydrophilic interaction chromatography - high-resolution mass spectrometry.

Untargeted metabolomics of human plasma with mass spectrometry is of particular interest in medical research to explore pathophysiology, find disease biomarkers or for the understanding of the response to pharmacotherapy. Since analytical performances may be impacted by the laboratory environment and the acquisition method settings, the objectives of this study were to assess the role of interfering compounds and to propose an acquisition method to maximize the metabolome coverage for human plasma metabolomic analysis. Human plasma samples were processed with liquid/liquid extraction then analysed with HILIC-high resolution mass spectrometry.

A marine-sourced fucoidan solution inhibits Toll-like-receptor-3-induced cytokine release by human bronchial epithelial cells.

Fucoidans are sulfated polysaccharides from brown algae, known to have immunomodulatory activity. Their effects on the response of airway epithelial cells to Toll-like receptor 3 (TLR3) stimulation have not been characterized. Our objective was to evaluate the effects of a marine-sourced fucoidan solution (MFS) on the TLR3-induced expression and/or production of cytokines and prostaglandin by human primary bronchial epithelial cells as a model of the airway epithelium.

The Role of Toll-Like Receptors in the Production of Cytokines by Human Lung Macrophages.

Background: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines.

CCR10 ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma.

Background: We previously showed that patients with severe allergic asthma have high numbers of circulating ILC2s expressing CCR10.

Method: Herein, CCR10 ILC2s were further analyzed in the blood of healthy individuals or patients with allergic and non-allergic asthma. Characteristics of human CCR10 and CCR10 ILC2s were assessed by flow cytometry as well as single-cell multiplex RT-qPCR.

Comparison of the in vitro pharmacological profiles of long-acting muscarinic antagonists in human bronchus.

Background And Purpose: Long-acting muscarinic antagonists (LAMAs) have been recommended for the treatment of chronic obstructive pulmonary disease and (more recently) asthma. However, the in vitro pharmacological profiles of the four LAMAs currently marketed (tiotropium, umeclidinium, aclidinium and glycopyrronium) have not yet been compared (relative to ipratropium) by using the same experimental approach.

Experimental Approach: With a total of 560 human bronchial rings, we investigated the antagonists' potency, onset and duration of action for inhibition of the contractile response evoked by electrical field stimulation.

Human lung and monocyte-derived macrophages differ with regard to the effects of β-adrenoceptor agonists on cytokine release.

Background: β-adrenoceptor agonists have been shown to reduce the lipopolysaccharide (LPS)-induced cytokine release by human monocyte-derived macrophages (MDMs). We compare the expression of β-adrenoceptors and the inhibitory effect of formoterol and salmeterol on the LPS-induced release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and a range of chemokines (CCL2, 3, 4, and IL-8) by human lung macrophages (LMs) and MDMs.

Methods: LMs were isolated from patients undergoing resection and MDMs were obtained from blood monocytes in the presence of GM-CSF.

In smokers, Sonic hedgehog modulates pulmonary endothelial function through vascular endothelial growth factor.

Background: Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers.

Metabolomics in the Diagnosis and Pharmacotherapy of Lung Diseases.

Metabolomics is of the increasing interests in medical research and the study of respiratory diseases. This novel type of small molecule analysis can be performed not only on conventional biological samples such as plasma or urine but also on sputum, bronchoalveolar fluid, exhaled breath condensate or exhaled breath itself (which is particularly relevant for research on respiratory diseases). On one hand, powerful analytical methodologies (including mass spectrometry and nuclear magnetic resonance spectroscopy) are labour-intensive but enable the exhaustive identification of metabolites.

The impact of low-frequency, low-force cyclic stretching of human bronchi on airway responsiveness.

Background: In vivo, the airways are constantly subjected to oscillatory strain (due to tidal breathing during spontaneous respiration) and (in the event of mechanical ventilation) positive pressure. This exposure is especially problematic for the cartilage-free bronchial tree. The effects of cyclic stretching (other than high-force stretching) have not been extensively characterized.

In allergic rhinitis, work, classroom and activity impairments are weakly related to other outcome measures.

Background: The impact of grass pollen-induced allergic rhinitis (AR) on classroom/work productivity and activities can be assessed with a specific instrument: the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI-AS). This study evaluated the relationships between the WPAI-AS and other outcome measures in AR.

Methods: Adolescents (aged 12-17) and adults (aged 18-65) consulting specialists for AR were enrolled in a four-week, multicentre, observational study.

The pharmacology of bitter taste receptors and their role in human airways.

The receptors involved in bitter taste perception (bitter taste receptors--T2Rs) constitute a family of G-protein-coupled receptors, of which around 29 subtypes have been identified in humans. T2R expression was initially thought to be confined to the oral cavity but has recently been described in a range of other tissues (such as the heart, gut, nasal cavity and lungs) and cell types (chemosensory, smooth muscle, endothelial, epithelial and inflammatory cells). Although it is still not clear whether endogenous T2R agonists exist, the T2R receptors recognize many natural and synthetic compounds, such as the acyl-homoserine lactones produced by bacteria, caffeine, chloroquine, and erythromycin.

Characterization of V0162, a new long-acting antagonist at human M3 muscarinic acetylcholine receptors.

The anticholinergic properties of the mequitazine enantiomer V0162 make it a drug candidate for the treatment of chronic obstructive airway diseases. Here, we compared V0162's in vitro pharmacological activity at recombinant human M3 muscarinic acetylcholine receptors (hM3Rs) with that of other anticholinergics, using (i) a radioligand binding assay, (ii) a functional reporter gene assay and (iii) a bronchoconstriction inhibition assay on human bronchial preparations. V0162 had high affinity for hM3Rs, with a pKi varying from 9.