Publications
Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleKolsum U, Donaldson GC, Singh R, et al., 2017,
Blood and sputum eosinophils in COPD; relationship with bacterial load
, Respiratory Research, Vol: 18, ISSN: 1465-993XBACKGROUND: Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients. Bacterial infection causes increased airway neutrophilic inflammation. The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain. We tested the hypothesis that bacterial load and eosinophil counts are inversely related. METHODS: COPD patients were seen at stable state and exacerbation onset. Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae. PPM positive was defined as total load ≥1 × 10(4)copies/ml. Sputum and whole blood were analysed for differential cell counts. RESULTS: At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs. 1.25% respectively, p = 0.01). Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 10(9)/L vs. 0.23 × 10(9)/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples. CONCLUSIONS: These findings indicate an inverse relationship between bacterial infection and eosinophil counts. Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.
-
Journal articleWang K, Milojevic N, Sheinman B, et al., 2017,
Cough management in primary, secondary and tertiary settings
, Pulmonary Pharmacology & Therapeutics, Vol: 47, Pages: 93-98, ISSN: 1522-9629This review reflects upon the management of cough in primary, secondary and tertiary care settings. It reviews the burden of cough, the diagnostic tools employed to investigate the cause of cough and pragmatic treatment strategies. A clinical case vignette presenting in primary care highlights the challenges of managing cough by family practitioners. An approach to establishing a persistent cough clinic service in secondary care is described. Finally, the entity of idiopathic cough in tertiary care and the specialist approaches to treating recalcitrant cough are addressed.
-
Journal articleSimpson AJ, Honkoop PJ, Kennington E, et al., 2017,
Perspectives of patients and healthcare professionals on mHealth for asthma self-management
, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936Mobile healthcare (mHealth) has the potential to revolutionise the self-management of long-term medical conditions such as asthma. A user-centred design is integral if mHealth is to be embraced by patients and healthcare professionals.The aim of this study was to determine the perspectives of individuals with asthma and healthcare professionals on the use of mHealth for asthma self-management.We used a sequential exploratory mixed methods design; focus groups informed the development of questionnaires, which were disseminated to individuals with asthma and healthcare professionals.Focus group participants (18 asthma patients and five healthcare professionals) identified 12 potential uses of mHealth. Questionnaire results showed that individuals with asthma (n=186) most frequently requested an mHealth system to monitor asthma over time (72%) and to collect data to present to healthcare teams (70%). In contrast, healthcare professionals (n=63) most frequently selected a system alerting patients to deteriorating asthma control (86%) and advising them when to seek medical attention (87%). Individuals with asthma were less likely than healthcare professionals (p<0.001) to believe that assessing medication adherence and inhaler technique could improve asthma control.Our data provide strong support for mHealth for asthma self-management, but highlight fundamental differences between the perspectives of patients and healthcare professionals.
-
Journal articleRoche N, Chapman KR, Vogelmeier CF, et al., 2017,
Blood Eosinophils and response to maintenance COPD treatment: data from the FLAME trial
, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 1189-1197, ISSN: 1535-4970Rationale: Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD).Objectives: We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting β2-agonist combination versus a long-acting β2-agonist/long-acting muscarinic antagonist combination for exacerbation prevention.Methods: We conducted prespecified analyses of data from the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone Salmeterol on COPD Exacerbations) study, which compared once-daily long-acting β2-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 μg with twice-daily long-acting β2-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 μg in patients with one or more exacerbations in the preceding year. Subsequent post hoc analyses were conducted to address further cutoffs and endpoints.Measurements and Main Results: We compared treatment efficacy according to blood eosinophil percentage (<2% and ≥2%, <3% and ≥3%, and <5% and ≥5%) and absolute blood eosinophil count (<150 cells/μl, 150 to <300 cells/μl, and ≥300 cells/μl). Indacaterol/glycopyrronium was significantly superior to salmeterol/fluticasone for the prevention of exacerbations (all severities, or moderate or severe) in the <2%, ≥2%, <3%, <5%, and <150 cells/μl subgroups, and at no cutoff was salmeterol/fluticasone superior to indacaterol/glycopyrronium. Furthermore, the rate of moderate or severe exacerbations did not increase with increasing blood eosinophils. The incidence of pneumonia was higher in patients receiving salmeterol/fluticasone than indacaterol/glycopyrronium in both the <2% and ≥2% subgroups.Conclusions: Our prospective analyses indicate that indacaterol/glycopyrronium provides superior or s
-
Journal articleWedzicha JA, Brochard LJ, Martinez FD, et al., 2017,
The long view and the fast lane
, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 1081-1139, ISSN: 1535-4970 -
Journal articleEdwards MR, Saglani S, Schwarze J, et al., 2017,
Addressing unmet needs in understanding asthma mechanisms: From the European Asthma Research and Innovation Partnership (EARIP) Work Package (WP)2 collaborators
, European Respiratory Journal, Vol: 49, ISSN: 1399-3003Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European productivity. There is a wide spectrum of disease severity and control. Therapeutic advances have been slow despite greater understanding of basic mechanisms and the lack of satisfactory preventative and disease modifying management for asthma constitutes a significant unmet clinical need. Preventing, treating and ultimately curing asthma requires co-ordinated research and innovation across Europe. The European Asthma Research and Innovation Partnership (EARIP) is an FP7-funded programme which has taken a co-ordinated and integrated approach to analysing the future of asthma research and development. This report aims to identify the mechanistic areas in which investment is required to bring about significant improvements in asthma outcomes.
-
Journal articleToussaint M, Swieboda D, Guedan A, et al., 2017,
NETosis and associated host DNA orchestrate rhinovirus-induced type 2 allergic asthma exacerbation
, Nature Medicine, ISSN: 1546-170XRespiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of type 2 immunity is strongly implicated in asthma exacerbation, but how virus infection boosts type 2 responses during exacerbation is poorly understood. We report a significant correlation between release of host double stranded DNA (dsDNA) following rhinovirus infection and exacerbation of type 2 allergic inflammation and disease severity in patients. In a mouse model, we show that rhinovirus infection triggers neutrophil extracellular traps (NETs) formation and host dsDNA release. We further demonstrate that inhibiting NETosis by blocking neutrophil elastase or degrading NETs with DNase protects mice from type 2 allergic asthma exacerbations. Furthermore, injection of host dsDNA alone is sufficient to recapitulate many features of rhinovirus-induced type 2 immune responses and asthma pathology. Thus, NETosis and host dsDNA contribute to exacerbation pathogenesis and may represent potential targets for novel treatments of rhinovirus-induced asthma exacerbations.
-
Journal articleHind M, Polkey MI, Simonds AK, 2017,
Homeward bound: a centenary of home mechanical ventilation
, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 1140-1149, ISSN: 1073-449XThe evolution of home mechanical ventilation is an intertwined chronicle of negative and positive pressure modes and their role in managing ventilatory failure in neuromuscular diseases and other chronic disorders. The uptake of noninvasive positive pressure ventilation has resulted in widespread growth in home ventilation internationally and fewer patients being ventilated invasively. As with many applications of domiciliary medical technology, home ventilatory support has either led or run in parallel with acute hospital applications and has been influenced by medical and societal shifts in the approach to chronic care, the creation of community support teams, a preference of recipients to be treated at home, and economic imperatives. This review summarizes the trends and growing evidence base for ventilatory support outside the hospital.
-
Journal articleLee J, Donaldson AV, Lewis A, et al., 2017,
Circulating miRNAs from imprinted genomic regions are associated with peripheral muscle strength in COPD patients
, European Respiratory Journal, Vol: 49, Pages: 1-4, ISSN: 1399-3003 -
Journal articleMcAuley J, Taylor R, Simonds A, et al., 2017,
Respiratory difficulty with palatal, laryngeal and respiratory muscle tremor in adult-onset Alexander's disease.
, BMJ Case Rep, Vol: 2017Sleep apnoea and respiratory difficulties are reported in adult-onset Alexander's disease (AOAD), an autosomal-dominant leukodystrophy that presents mainly with progressive ataxia. We demonstrate for the first time that the respiratory symptoms can result from association of palatal tremor with a similar tremor of laryngeal and respiratory muscles that interrupts normal inspiration and expiration.A 60-year-old woman presented with progressive ataxia, palatal tremor and breathlessness. MRI revealed medullary atrophy, bilateral T2 hyperintensities in the dentate nuclei and hypertrophic olivary degeneration (HOD). AOAD was confirmed genetically with a positive glial fibrillary acidic protein (GFAP) mutation. Electrophysiological study revealed 1.5 Hz rhythmic laryngeal and respiratory muscle activity. Her respiratory symptoms were significantly improved at night with variable positive pressure ventilation.This case illustrates that palatal tremor in AOAD, and potentially in other conditions, may be associated with treatable breathlessness due to a similar tremor of respiratory muscles.
-
Journal articleConforti F, Davies ER, Calderwood CJ, et al., 2017,
The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis.
, Oncotarget, Vol: 8, Pages: 48737-48754, ISSN: 1949-2553Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects.
-
Journal articlePatrick Y, Lee A, Raha O, et al., 2017,
Effects of sleep deprivation on cognitive and physical performance in university students
, Sleep and Biological Rhythms, Vol: 15, Pages: 217-225, ISSN: 1446-9235Sleep deprivation is common among university students, and has been associated with poor academic performance and physical dysfunction. However, current literature has a narrow focus in regard to domains tested, this study aimed to investigate the effects of a night of sleep deprivation on cognitive and physical performance in students. A randomized controlled crossover study was carried out with 64 participants [58% male (n = 37); 22 ± 4 years old (mean ± SD)]. Participants were randomized into two conditions: normal sleep or one night sleep deprivation. Sleep deprivation was monitored using an online time-stamped questionnaire at 45 min intervals, completed in the participants’ homes. The outcomes were cognitive: working memory (Simon game© derivative), executive function (Stroop test); and physical: reaction time (ruler drop testing), lung function (spirometry), rate of perceived exertion, heart rate, and blood pressure during submaximal cardiopulmonary exercise testing. Data were analysed using paired two-tailed T tests and MANOVA. Reaction time and systolic blood pressure post-exercise were significantly increased following sleep deprivation (mean ± SD change: reaction time: 0.15 ± 0.04 s, p = 0.003; systolic BP: 6 ± 17 mmHg, p = 0.012). No significant differences were found in other variables. Reaction time and vascular response to exercise were significantly affected by sleep deprivation in university students, whilst other cognitive and cardiopulmonary measures showed no significant changes. These findings indicate that acute sleep deprivation can have an impact on physical but not cognitive ability in young healthy university students. Further research is needed to identify mechanisms of change and the impact of longer term sleep deprivation in this population.
-
Journal articlePavitt MJ, Swanton LL, Hind M, et al., 2017,
Choking on a foreign body: a physiological study of the effectiveness of abdominal thrust manoeuvres to increase thoracic pressure
, THORAX, Vol: 72, Pages: 576-578, ISSN: 0040-6376The Heimlich manoeuvre is a well-known intervention for the management of choking due to foreign body airway occlusion, but the evidence base for guidance on this topic is limited and guidelines differ. We measured pressures during abdominal thrusts in healthy volunteers. The angle at which thrusts were performed (upthrust vs circumferential) did not affect intrathoracic pressure. Self-administered abdominal thrusts produced similar pressures to those performed by another person. Chair thrusts, where the subject pushed their upper abdomen against a chair back, produced higher pressures than other manoeuvres. Both approaches should be included in basic life support teaching.
-
Journal articleBaker K, Raemdonck K, Snelgrove RJ, et al., 2017,
Characterisation of a murine model of the late asthmatic response
, Respiratory Research, Vol: 18, ISSN: 1465-9921Background: The incidence of asthma is increasing at an alarming rate. While the current available therapies areeffective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In thesearch to understand disease pathogenesis and find effective therapies hypotheses are often tested in animalmodels before progressing into clinical studies. However, current dogma is that animal model data is often notpredictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challengeinduced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal modelsystems. As the mouse is typically selected as preferred species for pre-clinical models, we wanted to characteriseand probe the validity of a murine model exhibiting an allergen induced LAR.Methods: C57BL/6 mice were sensitised with antigen and subsequently topically challenged with the sameantigen. The role of AlumTM adjuvant, glucocorticoid, long acting muscarinic receptor antagonist (LAMA), TRPA1,CD4+ and CD8+ T cells, B cells, Mast cells and IgE were determined in the LAR using genetically modified mice anda range of pharmacological tools.Results: Our data showed that unlike other features of asthma (e.g. cellular inflammation, elevated IgE levels andairway hyper-reactivity (AHR) the LAR required AlumTMadjuvant. Furthermore, the LAR appeared to be sensitive toglucocorticoid and required CD4+ T cells. Unlike in other species studied, the LAR was not sensitive to LAMAtreatment nor required the TRPA1 ion channel, suggesting that airway sensory nerves are not involved in the LARin this species. Furthermore, the data suggested that CD8+ T cells and the mast cell—B-cell - IgE axis appear to beprotective in this murine model.Conclusion: Together we can conclude that this model does feature steroid sensitive, CD4+ T cell dependent,allergen induced LAR. However, collectively our data questions the validit
-
Journal articleDemeyer H, Louvaris Z, Frei A, et al., 2017,
Physical activity is increased by a 12 week semi-automated telecoaching program in patients with COPD, a multicenter randomized controlled trial
, Thorax, Vol: 72, Pages: 415-423, ISSN: 1468-3296RationaleReduced physical activity (PA) in patients with COPD is associated with a poor prognosis. Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group. ObjectivesTo investigate the effectiveness of a 12 week semi-automated telecoaching intervention on PA in COPD patients in a multicenter European RCT. Methods343 patients from 6 centers, including a wide disease spectrum, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014. This 12 weeks intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application. The latter provided an individualized daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators. Physical activity was measured using accelerometry during 1 week preceding randomization and during week 12. Secondary outcomes included exercise capacity and health status. Analyses were based on intention-to-treat.Main resultsBoth groups were comparable at baseline in terms of factors influencing PA. At 12 weeks, the intervention yielded a between group difference of mean, 95% [ll-ul] +1469, 95% [971 – 1965] steps.day-1 and +10.4, 95% [6.1 - 14.7] min.day-1 moderate physical activity; favoring the IG (all p≤0.001). The change in six minute walk distance was significantly different (13.4, 95% [3.40 - 23.5]m, p<0.01), favoring the IG. In IG patients an improvement could be observed in the functional state domain of the CCQ (p=0.03), when compared to UCG. Other health status outcomes did not differ.ConclusionsThe amount and intensity of PA can be significantly increased in COPD patients using a 12 week semi-automated telecoaching intervention including a stepcounter and an application installed on a smartphone.
-
Journal articlePereno V, Carugo D, Bau L, et al., 2017,
Electroformation of giant unilamellar vesicles on stainless steel electrodes
, ACS Omega, Vol: 2, Pages: 994-1002, ISSN: 2470-1343Giant unilamellar vesicles (GUVs) are well-established model systems forstudying membrane structure and dynamics. Electroformation, also referred to aselectroswelling, is one of the most prevalent methods for producing GUVs, as it enablesmodulation of the lipid hydration process to form relatively monodisperse, defect-freevesicles. Currently, however, it is expensive and time-consuming compared with othermethods. In this study, we demonstrate that 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine GUVs can be prepared readily at a fraction of the cost on stainless steel electrodes,such as commercially available syringe needles, without any evidence of lipid oxidationor hydrolysis.
-
Journal articleTunstall T, Kon OM, Bartlett N, et al., 2017,
A Comprehensive Evaluation of Nasal and Bronchial Cytokines and Chemokines Following Experimental Rhinovirus Infection in Allergic Asthma: Increased Interferons (IFN-γ and IFN-λ) and Type 2 Inflammation (IL-5 and IL-13)
, EBioMedicine, Vol: 19, Pages: 128-138, ISSN: 2352-3964BackgroundRhinovirus infection is a major cause of asthma exacerbations.ObjectivesWe studied nasal and bronchial mucosal inflammatory responses during experimental rhinovirus-induced asthma exacerbations.MethodsWe used nasosorption on days 0, 2–5 and 7 and bronchosorption at baseline and day 4 to sample mucosal lining fluid to investigate airway mucosal responses to rhinovirus infection in patients with allergic asthma (n = 28) and healthy non-atopic controls (n = 11), by using a synthetic absorptive matrix and measuring levels of 34 cytokines and chemokines using a sensitive multiplex assay.ResultsFollowing rhinovirus infection asthmatics developed more upper and lower respiratory symptoms and lower peak expiratory flows compared to controls (all P < 0.05). Asthmatics also developed higher nasal lining fluid levels of an anti-viral pathway (including IFN-γ, IFN-λ/IL-29, CXCL11/ITAC, CXCL10/IP10 and IL-15) and a type 2 inflammatory pathway (IL-4, IL-5, IL-13, CCL17/TARC, CCL11/eotaxin, CCL26/eotaxin-3) (area under curve day 0–7, all P < 0.05). Nasal IL-5 and IL-13 were higher in asthmatics at day 0 (P < 0.01) and levels increased by days 3 and 4 (P < 0.01). A hierarchical correlation matrix of 24 nasal lining fluid cytokine and chemokine levels over 7 days demonstrated expression of distinct interferon-related and type 2 pathways in asthmatics. In asthmatics IFN-γ, CXCL10/IP10, CXCL11/ITAC, IL-15 and IL-5 increased in bronchial lining fluid following viral infection (all P < 0.05).ConclusionsPrecision sampling of mucosal lining fluid identifies robust interferon and type 2 responses in the upper and lower airways of asthmatics during an asthma exacerbation. Nasosorption and bronchosorption have potential to define asthma endotypes in stable disease and at exacerbation.
-
Journal articleChung KF, Seiffert J, Chen S, et al., 2017,
Inactivation, clearance, and functional effects of lung-instilled short and long silver nanowires in rats
, ACS Nano, Vol: 11, Pages: 2652-2664, ISSN: 1936-086XThere is a potential for silver nanowires (AgNWs) to be inhaled, but there is little information on their health effects and their chemical transformation inside the lungs in vivo. We studied the effects of short (S-AgNWs; 1.5 μm) and long (L-AgNWs; 10 μm) nanowires instilled into the lungs of Sprague–Dawley rats. S- and L-AgNWs were phagocytosed and degraded by macrophages; there was no frustrated phagocytosis. Interestingly, both AgNWs were internalized in alveolar epithelial cells, with precipitation of Ag2S on their surface as secondary Ag2S nanoparticles. Quantitative serial block face three-dimensional scanning electron microscopy showed a small, but significant, reduction of NW lengths inside alveolar epithelial cells. AgNWs were also present in the lung subpleural space where L-AgNWs exposure resulted in more Ag+ve macrophages situated within the pleura and subpleural alveoli, compared with the S-AgNWs exposure. For both AgNWs, there was lung inflammation at day 1, disappearing by day 21, but in bronchoalveolar lavage fluid (BALF), L-AgNWs caused a delayed neutrophilic and macrophagic inflammation, while S-AgNWs caused only acute transient neutrophilia. Surfactant protein D (SP-D) levels in BALF increased after S- and L-AgNWs exposure at day 7. L-AgNWs induced MIP-1α and S-AgNWs induced IL-18 at day 1. Large airway bronchial responsiveness to acetylcholine increased following L-AgNWs, but not S-AgNWs, exposure. The attenuated response to AgNW instillation may be due to silver inactivation after precipitation of Ag2S with limited dissolution. Our findings have important consequences for the safety of silver-based technologies to human health.
-
Journal articlePetrova NV, Emelyanova AG, Gorbunov EA, et al., 2017,
Efficacy of novel antibody-based drugs against rhinovirus infection: In vitro and in vivo results
, ANTIVIRAL RESEARCH, Vol: 142, Pages: 185-192, ISSN: 0166-3542 -
Journal articleShim JM, Lee JS, Russell KE, et al., 2017,
BET proteins are a key component of immunoglobulin gene expression
, Epigenomics, Vol: 9, Pages: 393-406, ISSN: 1750-192XAims:Bromo and extraterminal domain (BET) proteins have been shown to regulate gene expression including inflammatory genes. Methods:In order to investigate the role of the BET proteins in immunoglobulin production we treated the human B cell line CLNH11.4 and primary human B cells and ozone exposed mice with BET inhibitors (JQ1 or IBET151). Results:Both proliferation and IgG production were reduced by JQ1 in a concentration-dependent manner. JQ1 significantly reduced immunoglobulin gene transcription. In vivo treatment of ozone-exposed mice with the BET inhibitor IBET151 similarly inhibited ozone induced immunoglobulin production. JQ1 did not reduce the protein levels of Brd4 or Oct2 per se but reduced the ability of Brd4 and Oct2 to co-immunoprecipitate and of Oct2 to bind to immunoglobulin gene promoters.Conclusions:Our results indicate that BET proteins including Brd4 play a crucial role regulation B cell specific gene expression and immunoglobulin production.
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.