Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleMackay AJ, Patel ARC, Singh R, et al., 2017,
Randomized Double-Blind Controlled Trial of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease
, American Journal of Respiratory and Critical Care Medicine, Vol: 196, Pages: 656-659, ISSN: 1073-449X -
Journal articleReuschl AK, Edwards MR, Parker R, et al., 2017,
Innate activation of human primary epithelial cells broadens the host response to Mycobacterium tuberculosis in the airways
, PLoS Pathogens, Vol: 13, ISSN: 1553-7366Early events in the human airways determining whether exposure to Mycobacterium tuberculosis (Mtb) results in acquisition of infection are poorly understood. Epithelial cells are the dominant cell type in the lungs, but little is known about their role in tuberculosis. We hypothesised that human primary airway epithelial cells are part of the first line of defense against Mtb-infection and contribute to the protective host response in the human respiratory tract. We modelled these early airway-interactions with human primary bronchial epithelial cells (PBECs) and alveolar macrophages. By combining in vitro infection and transwell co-culture models with a global transcriptomic approach, we identified PBECs to be inert to direct Mtb-infection, yet to be potent responders within an Mtb-activated immune network, mediated by IL1β and type I interferon (IFN). Activation of PBECs by Mtb-infected alveolar macrophages and monocytes increased expression of known and novel antimycobacterial peptides, defensins and S100-family members and epithelial-myleoid interactions further shaped the immunological environment during Mtb-infection by promoting neutrophil influx. This is the first in depth analysis of the primary epithelial response to infection and offers new insights into their emerging role in tuberculosis through complementing and amplifying responses to Mtb.
-
Journal articleUpton N, Jackson DJ, Nikonova AA, et al., 2017,
Rhinovirus induction of fractalkine (CX3CL1) in airway and peripheral blood mononuclear cells in asthma
, PLoS ONE, Vol: 12, ISSN: 1932-6203Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1) and pathogenic (type 2) responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1) fractalkine is produced in airway cells and in peripheral blood leucocytes, (2) rhinovirus infection increases production of fractalkine and (3) levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from non-asthmatic controls (n = 15) and mild allergic asthmatic (n = 15) subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1) and M2 (type 2) macrophages and in BAL fluid obtained from mild (n = 11) and moderate (n = 14) allergic asthmatic and non-asthmatic control (n = 10) subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P<0.01) and in M1-polarised macrophages (P<0.05), but not in BAL cells from mild asthmatics or in M2 polarised macrophages. Rhinovirus induced fractalkine in PBMCs from asthmatic (P<0.001) and healthy control subjects (P<0.05). Trends towards induction of fractalkine in moderate asthmatic subjects during in vivo rhinovirus infection failed to reach statistical significance. Fractalkine may be involved in both immunopathological and anti-viral immune responses to rhinovirus infection. Further investigation into how fractalkine is regulated across different cell types and into the effect of stimulation including rhinovirus infection is warranted to better understand the precise role of this unique dual adhesion factor and chemokine in immune cell recruitment.
-
Journal articleRoux BT, Heward JA, Donnelly LE, et al., 2017,
Catalog of Differentially Expressed Long Non-Coding RNA following Activation of Human and Mouse Innate Immune Response
, Frontiers in Immunology, Vol: 8, ISSN: 1664-3224Despite increasing evidence to indicate that long non-coding RNAs (lncRNAs) are novel regulators of immunity, there has been no systematic attempt to identify and characterize the lncRNAs whose expression is changed following the induction of the innate immune response. To address this issue, we have employed next-generation sequencing data to determine the changes in the lncRNA profile in four human (monocytes, macrophages, epithelium, and chondrocytes) and four mouse cell types (RAW 264.7 macrophages, bone marrow-derived macrophages, peritoneal macrophages, and splenic dendritic cells) following exposure to the pro-inflammatory mediators, lipopolysaccharides (LPS), or interleukin-1β. We show differential expression of 204 human and 210 mouse lncRNAs, with positional analysis demonstrating correlation with immune-related genes. These lncRNAs are predominantly cell-type specific, composed of large regions of repeat sequences, and show poor evolutionary conservation. Comparison within the human and mouse sequences showed less than 1% sequence conservation, although we identified multiple conserved motifs. Of the 204 human lncRNAs, 21 overlapped with syntenic mouse lncRNAs, of which five were differentially expressed in both species. Among these syntenic lncRNA was IL7-AS (antisense), which was induced in multiple cell types and shown to regulate the production of the pro-inflammatory mediator interleukin-6 in both human and mouse cells. In summary, we have identified and characterized those lncRNAs that are differentially expressed following activation of the human and mouse innate immune responses and believe that these catalogs will provide the foundation for the future analysis of the role of lncRNAs in immune and inflammatory responses.
-
Journal articleHaldar K, Bafadhel M, Lau K, et al., 2017,
Microbiome balance in sputum determined by PCR stratifies COPD exacerbations and shows potential for selective use of antibiotics
, PLOS ONE, Vol: 12, ISSN: 1932-6203- Author Web Link
- Cite
- Citations: 23
-
Journal articleRossios C, Pavlidis S, Gibeon D, et al., 2017,
Impaired innate immune gene profiling in airway smooth muscle cells from chronic cough patients.
, Bioscience Reports, ISSN: 0144-8463Chronic cough is associated with airway inflammation and remodelling. Abnormal airway smooth muscle cell (ASMC) function may underlie mechanisms of chronic cough. Our objective was to examine the transcriptome and focused secretome of ASMCs from chronic cough patients and healthy non-cough volunteers. ASMC gene expression profiling was performed at baseline and/or after stimulation with polyinosinic:polycytidylic acid (poly(I:C)) to mimic viral infection. Supernatants were collected for multiplex analysis. Our results showed no significant differentially expressed genes (DEGs, false discovery rate: FDR<0.05) between chronic cough and healthy non-cough ASMCs at baseline. Poly(I:C) stimulation resulted in 212 DEGs (>1.5 fold change, FDR <0.05) in ASMCs from chronic cough patients compared with 1674 DEGs in healthy non-cough volunteers. The top up-regulated genes included CXCL11 , CXCL10 , CCL5 and IFI44L corresponding with inflammation and innate immune response pathways. ASMCs from cough subjects had enhanced activation of viral response pathways in response to poly(I:C) compared to healthy non-cough subjects, reduced activation of pathways involved in chronic inflammation and equivalent activation of neuroregulatory genes. The poly(I:C)-induced release of inflammatory mediators, including CXCL8, IL-6 and CXCL1, from ASMCs from cough patients was significantly impaired compared to healthy non-cough subjects. Addition of fluticasone propionate (FP) to poly(I:C)-treated ASMCs resulted in greater gene expression changes in healthy non-cough ASMCs. FP had a differential effect on poly(I:C)-induced mediator release between chronic cough and healthy non-cough volunteers. In conclusion, altered innate immune and inflammatory gene profiles within ASMCs, rather than infiltrating cells or nerves, may drive the cough response following respiratory viral infection.
-
Journal articleAllinson JP, Wedzicha JA, 2017,
Update in Chronic Obstructive Pulmonary Disease 2016
, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 196, Pages: 414-424, ISSN: 1073-449XChronic obstructive pulmonary disease (COPD) describes a predominantly smoking-induced small airway and/or emphysematous disease associated with airflow limitation. Considered progressive, irreversible, and responsible for substantial morbidity and mortality worldwide, COPD remains the subject of vigorous study, and advances made during 2016 are already reflected in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines (1). Researchers continue to explore strategies, pharmacological or otherwise, to improve the lives of those who have developed this condition; and it is hoped, by improving phenotyping of this heterogeneous disease, that we might ultimately deliver personalized medicine. Debate remains over how to identify undiagnosed COPD in individuals who would benefit from intervention, while avoiding overdiagnosis, and these controversies perhaps highlight shortcomings in accepted disease definitions. Not unrelatedly, renewed interest has emerged in explaining why some individuals develop COPD and identifying the formative stages of COPD development.
-
Journal articlefarre garros, paul R, connolly M, et al., 2017,
miR-542 promotes mitochondrial dysfunction and SMAD activity and is raised in ICU Acquired Weakness
, American Journal of Respiratory and Critical Care Medicine, Vol: 196, Pages: 1-12, ISSN: 1073-449XRationale: Loss of skeletal muscle mass and function is a common consequence of critical illness and a range of chronic diseases but the mechanisms by which this occurs are unclear. Objectives: We aimed to identify miRNAs that were increased in the quadriceps of patients with muscle wasting and to determine the molecular pathways by which they contributed to muscle dysfunction. Methods: miR-542-3p/-5p were quantified in the quadriceps of patients with COPD and intensive care unit acquired weakness (ICUAW). The effect of miR-542-3p/5p was determined on mitochondrial function and TGF-β signaling in vitro and in vivo. Measurements and main results: miR-542-3p/5p were elevated in patients with COPD but more markedly in patients with ICUAW. In vitro, miR-542-3p suppressed the expression of the mitochondrial ribosomal protein MRPS10, and reduced 12S rRNA expression suggesting mitochondrial ribosomal stress. miR-542-5p increased nuclear phospho-SMAD2/3 and suppressed expression of SMAD7, SMURF1 and PPP2CA, proteins that inhibit or reduce SMAD2/3 phosphorylation suggesting that miR-542-5p increased TGF-β signaling. In mice, miR-542 over-expression caused muscle wasting, reduced mitochondrial function, 12S rRNA expression and SMAD7 expression, consistent with the effects of the miRNAs in vitro. Similarly, in patients with ICUAW, the expression of 12S rRNA and of the inhibitors of SMAD2/3 phosphorylation were reduced, indicative of mitochondrial ribosomal stress and increased TGF-β signaling. In patients undergoing aortic surgery, pre-operative levels of miR-542-3p/5p were positively correlated with muscle loss following surgery. Conclusion; Elevated miR-542-3p/5p may cause muscle atrophy in ICU patients through the promotion of mitochondrial dysfunction and activation of SMAD2/3 phosphorylation.
-
Journal articleEdwards MR, Walton RP, Jackson DJ, et al., 2017,
The potential of anti-infectives and immunomodulators as therapies for asthma and asthma exacerbations.
, Allergy, Vol: 73, Pages: 50-63, ISSN: 0105-4538Asthma is responsible for approximately 25,000 deaths annually in Europe despite available medicines that maintain asthma control and reduce asthma exacerbations. Better treatments are urgently needed for the control of chronic asthma and reduction in asthma exacerbations, the major cause of asthma mortality. Much research spanning >20 years shows a strong association between microorganisms including pathogens in asthma onset, severity and exacerbation, yet with the exception of antibiotics, few treatments are available that specifically target the offending pathogens. Recent insights into the microbiome suggest that modulating commensal organisms within the gut or lung may also be a possible way to treat/prevent asthma. The European Academy of Allergy & Clinical Immunology Task Force on Anti-infectives in Asthma was initiated to investigate the potential of anti-infectives and immunomodulators in asthma. This review provides a concise summary of the current literature and aimed to identify and address key questions that concern the use of anti-infectives and both microbe- and host-based immunomodulators and their feasibility for use in asthma.
-
Journal articleBelvisi MG, Birrell MA, 2017,
The emerging role of transient receptor potential channels in chronic lung disease
, EUROPEAN RESPIRATORY JOURNAL, Vol: 50, ISSN: 0903-1936- Author Web Link
- Cite
- Citations: 41
-
Journal articleMesquita R, Spina G, Pitta F, et al., 2017,
Physical activity patterns and clusters in 1001 patients with COPD
, Chronic Respiratory Disease, Vol: 14, Pages: 256-269, ISSN: 1479-9723We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.
-
Journal articleGoverdovsky V, von Rosenberg W, Nakamura T, et al., 2017,
Hearables: multimodal physiological in-ear sensing
, Scientific Reports, Vol: 7, ISSN: 2045-2322Future health systems require the means to assess and track the neural and physiological function of a user over long periods of time, and in the community. Human body responses are manifested through multiple, interacting modalities – the mechanical, electrical and chemical; yet, current physiological monitors (e.g. actigraphy, heart rate) largely lack in cross-modal ability, are inconvenient and/or stigmatizing. We address these challenges through an inconspicuous earpiece, which benefits from the relatively stable position of the ear canal with respect to vital organs. Equipped with miniature multimodal sensors, it robustly measures the brain, cardiac and respiratory functions. Comprehensive experiments validate each modality within the proposed earpiece, while its potential in wearable health monitoring is illustrated through case studies spanning these three functions. We further demonstrate how combining data from multiple sensors within such an integrated wearable device improves both the accuracy of measurements and the ability to deal with artifacts in real-world scenarios.
-
Journal articlePaschalaki KE, Zampetaki A, Baker JR, et al., 2017,
Downregulation of MicroRNA-126 Augments DNA Damage Response in Cigarette Smokers and COPD Patients.
, Am J Respir Crit Care Med -
Journal articleMao B, Calatayud DG, Mirabello V, et al., 2017,
Fluorescence-lifetime imaging and super-resolution microscopies shed light on the directed- and self-assembly of functional porphyrins onto carbon nanotubes and flat surfaces
, Chemistry - A European Journal, Vol: 23, Pages: 9772-9789, ISSN: 0947-6539Functional porphyrins have attracted intense attention due to their remarkably high extinction coefficients in the visible region and potential for optical and energy‐related applications. Two new routes to functionalised SWNTs have been established using a bulky ZnII‐porphyrin featuring thiolate groups at the periphery. We probed the optical properties of this zinc(II)‐substituted, bulky aryl porphyrin and those of the corresponding new nano‐composites with single walled carbon nanotube (SWNTs) and coronene, as a model for graphene. We report hereby on: i) the supramolecular interactions between the pristine SWNTs and ZnII‐porphyrin by virtue of π–π stacking, and ii) a novel covalent binding strategy based on the Bingel reaction. The functional porphyrins used acted as dispersing agent for the SWNTs and the resulting nanohybrids showed improved dispersibility in common organic solvents. The synthesized hybrid materials were probed by various characterisation techniques, leading to the prediction that supramolecular polymerisation and host–guest functionalities control the fluorescence emission intensity and fluorescence lifetime properties. For the first time, XPS studies highlighted the differences in covalent versus non‐covalent attachments of functional metalloporphyrins to SWNTs. Gas‐phase DFT calculations indicated that the ZnII‐porphyrin interacts non‐covalently with SWNTs to form a donor–acceptor complex. The covalent attachment of the porphyrin chromophore to the surface of SWNTs affects the absorption and emission properties of the hybrid system to a greater extent than in the case of the supramolecular functionalisation of the SWNTs. This represents a synthetic challenge as well as an opportunity in the design of functional nanohybrids for future sensing and optoelectronic applications.
-
Journal articleSimonds AK, 2017,
The Road Not Taken: Missed Opportunities in Managing Acute Exacerbations of Hypercapnic Respiratory Failure
, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 196, Pages: 124-125, ISSN: 1073-449X- Author Web Link
- Cite
- Citations: 1
-
Journal articleOsadnik CR, Tee VS, Carson-Chahhoud KV, et al., 2017,
Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease
, Cochrane Database of Systematic Reviews, Vol: 2017, ISSN: 1469-493XBackgroundNon-invasive ventilation (NIV) with bi-level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory failure (AHRF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).ObjectivesTo compare the efficacy of NIV applied in conjunction with usual care versus usual care involving no mechanical ventilation alone in adults with AHRF due to AECOPD. The aim of this review is to update the evidence base with the goals of supporting clinical practice and providing recommendations for future evaluation and research.Search methodsWe identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and PsycINFO, and through handsearching of respiratory journals and meeting abstracts. This update to the original review incorporates the results of database searches up to January 2017.Selection criteriaAll randomised controlled trials that compared usual care plus NIV (BiPAP) versus usual care alone in an acute hospital setting for patients with AECOPD due to AHRF were eligible for inclusion. AHRF was defined by a mean admission pH < 7.35 and mean partial pressure of carbon dioxide (PaCO2) > 45 mmHg (6 kPa). Primary review outcomes were mortality during hospital admission and need for endotracheal intubation. Secondary outcomes included hospital length of stay, treatment intolerance, complications, changes in symptoms, and changes in arterial blood gases.Data collection and analysisTwo review authors independently applied the selection criteria to determine study eligibility, performed data extraction, and determined risk of bias in accordance with Cochrane guideline
-
Journal articleBelvisi MG, Smith JA, 2017,
ATP and cough reflex hypersensitivity: a confusion of goals?
, European Respiratory Journal, Vol: 50, ISSN: 0903-1936 -
Conference paperNakamura T, adjei T, alqurashi Y, et al., 2017,
Complexity science for sleep stage classification from EEG
, IEEE International Joint Conference on Neural Networks (IJCNN) 2017, Publisher: IEEE, Pages: 4387-4394, ISSN: 2161-4407Automatic sleep stage classification is an importantparadigm in computational intelligence and promises consider-able advantages to the health care. Most current automatedmethods require the multiple electroencephalogram (EEG) chan-nels and typically cannot distinguish the S1 sleep stage fromEEG. The aim of this study is to revisit automatic sleep stageclassification from EEGs using complexity science methods. Theproposed method applies fuzzy entropy and permutation entropyas kernels of multi-scale entropy analysis. To account for sleeptransition, the preceding and following 30 seconds of epoch datawere used for analysis as well as the current epoch. Combiningthe entropy and spectral edge frequency features extracted fromone EEG channel, a multi-class support vector machine (SVM)was able to classify 93.8% of 5 sleep stages for the SleepEDFdatabase [expanded], with the sensitivity of S1 stage was 49.1%.Also, the Kappa’s coefficient yielded 0.90, which indicates almostperfect agreement.
-
Journal articleShaikh N, Johnson M, Hall D, et al., 2017,
Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle
, International Journal of Chronic Obstructive Pulmonary Disease, Vol: 12, Pages: 1903-1913, ISSN: 1176-9106Background: Intracellular mechanisms of action of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a long-acting β2-adrenoceptor (β2R) agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs).Materials and methods: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh]). Cyclic adenosine monophosphate (cAMP) was measured using an enzyme-linked immunosorbent assay, intracellular free calcium ([Ca2+]i) using a fluorescence assay, and regulator of G-protein signaling 2 (RGS2) messenger RNA using real-time quantitative polymerase chain reaction.Results: VI and salmeterol (10–12–10–6 M) induced cAMP production from ASMCs in a concentration-dependent manner, which was greater for VI at all concentrations. β2R antagonism by propranolol or ICI 118.551 (10–12–10–4 M) resulted in concentration-dependent inhibition of VI-induced cAMP production, and ICI 118.551 was more potent. MCh (5×10–6 M, 30 minutes) attenuated VI-induced cAMP production (P<0.05), whereas pretreatment with UMEC (10–8 M, 1 hour) restored the magnitude of VI-induced cAMP production. ASMC stimulation with MCh (10–11–5×10–6 M) resulted in a concentration-dependent increase in [Ca2+]i, which was attenuated with UMEC pretreatment. Reduction of MCh-induced [Ca2+]i release was greater with UMEC + VI versus UMEC. UMEC enhanced VI-induced RGS2 messenger RNA expression.Conclusion: These data indicate that UMEC reverses cholinergic inhibition of VI-induced cAMP production, and is a more potent muscarinic receptor antagonist when in combination with VI versus either alone.
-
Journal articleBonvini SJ, Belvisi MG, 2017,
Cough and airway disease: the role of ion channels
, Pulmonary Pharmacology and Therapeutics, Vol: 47, Pages: 21-28, ISSN: 1094-5539Cough is the most common reason for patients to visit a primary care physician, yet it remains an unmet medical need. It can be idiopathic in nature but can also be a troublesome symptom across chronic lung diseases such as asthma, COPD and idiopathic pulmonary fibrosis (IPF). Chronic cough affects up to 12% of the population and yet there are no safe and effective therapies. The cough reflex is regulated by vagal, sensory afferent nerves which innervate the airway. The Transient Receptor Potential (TRP) family of ion channels are expressed on sensory nerve terminals, and when activated can evoke cough. This review focuses on the role of 4 TRP channels; TRP Vannilloid 1 (TRPV1), TRP Ankyrin 1 (TRPA1), TRP Vannilloid 4 (TRPV4) and TRP Melastatin 8 (TRPM8) and the purinergic P2X3 receptor and their possible role in chronic cough. We conclude that these ion channels, given their expression profile and their role in the activation of sensory afferents and the cough reflex, may represent excellent therapeutic targets for the treatment of respiratory symptoms in chronic lung disease.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.