Publications
151 results found
Pruski P, MacIntyre DA, Lewis HV, et al., 2016, Medical swab analysis using desorption electrospray ionization mass spectrometry (DESI-MS) – a non-invasive approach for mucosal diagnostics, Analytical Chemistry, Vol: 89, Pages: 1540-1550, ISSN: 0003-2700
Medical swabs are routinely used worldwide to sample human mucosa for microbiological screening with culture methods. These are usually time-consuming and have a narrow focus on screening for particular microorganism species. As an alternative, direct mass spectrometric profiling of the mucosal metabolome provides a broader window into the mucosal ecosystem. We present for the first time a minimal effort/minimal-disruption technique for augmenting the information obtained from clinical swab analysis with mucosal metabolome profiling using desorption electrospray ionization mass spectrometry (DESI-MS) analysis. Ionization of mucosal biomass occurs directly from a standard rayon swab mounted on a rotating device and analyzed by DESI MS using an optimized protocol considering swab–inlet geometry, tip–sample angles and distances, rotation speeds, and reproducibility. Multivariate modeling of mass spectral fingerprints obtained in this way readily discriminate between different mucosal surfaces and display the ability to characterize biochemical alterations induced by pregnancy and bacterial vaginosis (BV). The method was also applied directly to bacterial biomass to confirm the ability to detect intact bacterial species from a swab. These results highlight the potential of direct swab analysis by DESI-MS for a wide range of clinical applications including rapid mucosal diagnostics for microbiology, immune responses, and biochemistry.
Gunawardana N, Campbell G, Lindsley S, et al., 2016, The effect of vitamin D supplementation on cathelicidin levels, vitamin D receptor (VDR) and E-cadherin expression after nasal allergen challenge in allergic rhinitis, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY-BLACKWELL, Pages: 1666-1666, ISSN: 0954-7894
Abbara A, Mahomed Z, Collin SM, et al., 2016, OLDER PATIENTS WITH TUBERCULOSIS HAVE LESS TYPICAL CHANGES ON CHEST RADIOGRAPHS, THORAX, Vol: 71, Pages: A143-A143, ISSN: 0040-6376
Abbara A, Hardman E, Collin SM, et al., 2016, THE NATURE AND DURATION OF SYMPTOMS AND TIME TO STARTING TREATMENT COMPARING OLDER WITH YOUNGER PULMONARY TUBERCULOSIS PATIENTS, THORAX, Vol: 71, Pages: A51-A52, ISSN: 0040-6376
Jha A, Dunning J, Tunstall T, et al., 2016, Asthma patients hospitalized with influenza lack mucosal and systemic type 2 inflammation, European Respiratory Society Congress, Publisher: European Respiratory Society, ISSN: 0903-1936
Background: Asthmatic persons tend to suffer from severe influenza, but the reasons for enhanced severity are unknown. Objectives: To determine the clinicopathological correlates of this susceptibility, we examined nasal and systemic immune responses in adults admitted to hospital with influenza-like illnesses. Methods: We studied 210 patients admitted with influenza-like illness at 11 hospitals in the UK across 2 winter seasons (2009/10 and 2010/11). Of these, 133 (63%) had confirmed influenza and 40/133 (30%) were asthmatic. We measured a panel of cytokines and chemokines in serum and nasal mucosal lining fluid and compared results in asthmatics, non-asthmatics and healthy control volunteers. Results: Asthma patients were more often female than non-asthmatics (70% vs 39% respectively), required less mechanical ventilation (15% vs 37.6%) and had shorter hospital stays (mean 8.3 vs 15.3 days, all P <0.05). Despite having equivalent nasopharyngeal influenza viral load, asthmatics had higher serum IFN-α levels but lower serum TNF-α, IL-5, IL-6 and CXCL8 (all P<0.05). In the nasal mucosa, asthmatics and non-asthmatics had comparable levels of soluble mediators. In particular, asthmatics showed no evidence of increased type 2 inflammation (IL-5 and IL-13) or deficient interferon responses. Conclusions: Adult asthmatics hospitalised with influenza show a propensity to be female with markedly reduced morbidity and systemic inflammation than non-asthmatics. Against expectation, asthmatics did not have increased type 2 inflammation. This study highlights the importance of defining underlying immune responses to infection in individual patients to enable future delivery of personalized therapy.
Minshall E, Patel H, Francis N, et al., 2016, Local chemokine profiling in eosinophilic esophagitis: the Synthetic Absorptive Matrix test, Pediatric Allergy and Immunology, Vol: 28, Pages: 100-102, ISSN: 1399-3038
We describe a novel method of sampling the esophageal lining fluid in children and show that levels of eotaxin-1 and MCP-4 differentiate those children with a histological diagnosis of EoE from those without. This article is protected by copyright. All rights reserved.
Leaker BR, Malkov VA, Mogg R, et al., 2016, The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1β), and complement, Mucosal Immunology, Vol: 10, Pages: 408-420, ISSN: 1935-3456
Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1β), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1β and MIP-1β/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1β; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.
Batista C, McIntosh M, Hansel T, et al., 2016, Elevated concentrations of CXCL8 in the nasal mucosal lining fluid of COPD patients as an accessible surrogate measure of bronchial levels, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Poletti D, Iannini V, Casolari P, et al., 2016, Nasal inflammation and its response to local glucocorticoid regular treatment in patients with persistent non-allergic rhinitis: a pilot study, Journal of Inflammation, Vol: 13, ISSN: 1476-9255
Background The pathogenesis of non-allergic rhinitis (NAR) is still largely unknown. Furthermore, it is unclear whether there is a correlation between the effect of nasal glucocorticoids on nasal inflammation and on nasal symptoms and quality of life. Methods In this pilot study we recruited 12 healthy subjects and 24 patients with recently diagnosed persistent NAR [12 untreated and 12 under regular treatment with nasal fluticasone furoate (two sprays of 27.5 µg each in each nostril once daily, total daily dose=110 µg) for at least 20 days]. Each subject filled a mini rhinoconjunctivitis quality of life questionnaire (mini RQLQ). Nasal scrapings were obtained from each subject and used to prepare slides for Diff-Quik and immunocytochemical staining for inflammatory and epithelial cells count, MUC5AC expression and the general pro-inflammatory transcription factor nuclear factor B (NF-B) activation. Results The nasal score of the mini RQLQ, the number of nasal inflammatory cells (neutrophils, eosinophils) and the number of goblet cells are significantly higher in untreated patients with persistent NAR compared with control subjects and treated NAR patients. The percentage of MUC5AC+ nasal epithelial cells is significantly increased in untreated patients with persistent NAR compared with the control subjects (41.8±6.4 vs 22.3±4.8, respectively; p=0.0403) without significant differences between control subjects and patients with persistent NAR on regular fluticasone furoate treatment with nasal glucocorticoids (33.9±5.0%; p=0.0604) nor between the 2 groups of persistent NAR subjects (p=0.3260). The number of cytosolic and/or nuclear p65+ nasal epithelial and inflammatory cells was not significantly different between the three groups. Conclusions Patients with persistent untreated NAR, compared with normal control subjects and patients with persistent NAR under regular treatment with nasal fluticasone furoate glucocorticoids by at lea
Jha A, Progatzky F, Wane M, et al., 2016, Human nasal mucosal responses to TLR agonists are mirrored by the zebrafish gill, British Association of Lung Research Summer Congress
Introduction: There are few reliable ways to study respiratory mucosal immune responses to viruses, viral-type toll-like receptor (TLR) agonists and vaccines. To investigate innate immune responses to TLR agonists (TLR3: poly IC/ poly ICLC; TLR7/8: resiquimod), we compared the effects on human nasal mucosa and zebrafish gills in vivo. Methods: Nasal challenge of adult volunteers was performed with saline, poly IC (n=4), poly ICLC (n=4) or resiquimod (n=8; 5 non-atopic, 3 atopic). Nasal mucosal lining fluid (MLF) was obtained by nasosorption at regular intervals up to 24 hours after challenge; nasal obstruction was monitored by peak nasal inspiratory flow (PNIF) and total nasal symptom scores (TNSS). Cytokines and interferons were measured in MLF using electrochemiluminescence on the Meso Scale Discovery (MSD) platform. Adult zebrafish gills were exposed to the same TLR agonists and gene expression was quantified in gill tissue at similar time-points. Results: Nasal challenge with TLR3 agonists failed to elicit any significant responses when compared to saline. In contrast resiquimod (10μg/100μl per nostril) caused a potent induction of cytokines with an early release (1-3 hours) of IFN-α2a, TNF-α and IL-1β and a later release (after 4 hours) of IFN-γ. The 3 volunteers with the highest levels of IFN-α2a were atopic. Six volunteers were asymptomatic and two volunteers had flu-like symptoms. There were no significant changes in clinical correlates of nasal obstruction. After resiquimod administration, but not TLR3 agonists, zebrafish gills showed an immune profile remarkably analogous to human nasal responses. Conclusion: The TLR7/8 agonist resiquimod is a potent mucosal inducer of IFN-α2a, IFN-γ and proinflammatory cytokines, whilst TLR3 agonists failed to stimulate mucosal innate immune responses. Zebrafish gills accurately mimic human nasal mucosal responses following exposure to TLR agonists, offering translational app
Gunawardana NC, Campbell G, Lindsley S, et al., 2016, The Effect of Vitamin D Supplementation on Mucosal IL-5, MMP9 and Cathelicidin after Nasal Allergen Challenge with Grass Pollen, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB73-AB73, ISSN: 0091-6749
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- Citations: 1
Dhariwal J, Cameron A, Trujillo-Torralbo B, et al., 2016, Novel Nasal Sampling Techniques Identify Ilc2s As Important Responders In Asthma During Nasal Allergen Challenge, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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- Citations: 2
Wolsk HM, Følsgaard NV, Birch S, et al., 2015, Picornavirus-Induced Airway Mucosa Immune Profile in Asymptomatic Neonates., Journal of Infectious Diseases, Vol: 213, Pages: 1262-1270, ISSN: 1537-6613
BACKGROUND: Bacterial airway colonization is known to alter the airway mucosa immune response in neonates whereas the impact of viruses is unknown. The objective was therefore to examine the effect of respiratory viruses on the immune signature in the airways of asymptomatic neonates. METHODS: Nasal aspirates from 571 asymptomatic 1-month-old neonates from the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort were investigated for respiratory viruses. Simultaneously, unstimulated airway mucosal lining fluid was obtained and quantified for levels of 20 immune mediators related to type 1, type 2, type 17, and regulatory immune paths. The association between immune mediator levels and viruses was tested by conventional statistics and partial least square discriminant analysis. RESULTS: Picornaviruses were detected in 58 neonates (10.2%) and other viruses in 10 (1.8%). A general up-regulation of immune mediators was found in the neonates with picornavirus (P < .0001; partial least square discriminant analysis). The association was pronounced for type 1- and type 2-related markers and was unaffected by comprehensive confounder adjustment. Detection of picornavirus and bacteria was associated with an additive general up-regulating effect. CONCLUSIONS: Asymptomatic presence of picornavirus in the neonatal airway is a potent activator of the topical immune response. This is relevant to understanding the immune potentiating effect of early life exposure to viruses.
Abbara A, Buell KG, Sullivan JAL, et al., 2015, TUBERCULOSIS IN OLDER VERSUS YOUNGER ADULT PATIENTS: A RETROSPECTIVE COMPARISON OF PATIENT CHARACTERISTICS AND TREATMENT OUTCOMES AT A MAJOR UK REFERRAL CENTRE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A203-A203, ISSN: 0040-6376
Abbara A, Lang S, Kon OM, et al., 2015, WEEKLY AUDIOGRAMS PRE-EMPTIVELY IDENTIFY AMIKACIN RELATED OTOTOXICITY IN MDR-TB, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A25-A25, ISSN: 0040-6376
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- Citations: 2
Dhariwal J, Kitson J, Jones RE, et al., 2015, Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness, PLOS One, Vol: 10, ISSN: 1932-6203
BackgroundPractical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide(LPS) is a component of the cell wall of Gram negative bacteria and a potentactivator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasalmucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levelsin mucosal lining fluid (MLF).MethodsWe performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy nonatopicsubjects (n = 14 per protocol). Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl) orplacebo were administered by a single nasal spray to each nostril. Using the recently developedmethod of nasosorption with synthetic adsorptive matrices (SAM), a series of sampleswere taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassayin MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1) was quantifiedfrom nasal epithelial curettage samples taken before and after challenge.ResultsTopical nasal LPS was well tolerated, causing no symptoms and no visible changes to thenasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8) and CCL3 (MIP-1α) (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μgLPS). At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05). Dose-relatedchanges in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophilsappeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levelsshowed prominent cytokine and chemokine responses to relatively low LPS doses (10μgand 30μg LPS).
Reed DM, Paschalaki KE, Starke RD, et al., 2015, An autologous endothelial cell: peripheral blood mononuclear cell assay that detects cytokine storm responses to biologics, The FASEB Journal, Vol: 29, Pages: 2595-2602, ISSN: 0892-6638
There is an urgent unmet need for human tissue bioassays to predict cytokine storm responses to biologics. Current bioassays that detect cytokine storm responses in vitro rely on endothelial cells, usually from umbilical veins or cell lines, cocultured with freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy adult volunteers. These assays therefore comprise cells from 2 separate donors and carry the disadvantage of mismatched tissues and lack the advantage of personalized medicine. Current assays also do not fully delineate mild (such as Campath) and severe (such as TGN1412) cytokine storm‐inducing drugs. Here, we report a novel bioassay where endothelial cells grown from stem cells in the peripheral blood (blood outgrowth endothelial cells) and PBMCs from the same donor can be used to create an autologous coculture bioassay that responds by releasing a plethora of cytokines to authentic TGN1412 but only modestly to Campath and not to control antibodies such as Herceptin, Avastin, and Arzerra. This assay performed better than the traditional mixed donor assay in terms of cytokine release to TGN1412 and, thus, we suggest provides significant advancement and a definitive system by which biologics can be tested and paves the way for personalized medicine.—Reed, D. M., Paschalaki, K. E., Starke, R. D., Mohamed, N. A., Sharp, G., Fox, B., Eastwood, D., Bristow, A., Ball, C., Vessillier, S., Hansel, T. T., Thorpe, S. J., Randi, A. M., Stebbings, R., Mitchell, J. A. An autologous endothelial cell:peripheral blood mononuclear cell assay that detects cytokine storm responses to biologics. FASEB J. 29, 2595‐2602 (2015). www.fasebj.org
Ross CL, Galloway-Phillipps N, Armstrong PC, et al., 2015, Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach, BMJ OPEN, Vol: 5, ISSN: 2044-6055
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- Citations: 3
Jayaraman A, Jackson DJ, Message SD, et al., 2014, IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection, MUCOSAL IMMUNOLOGY, Vol: 7, Pages: 1151-1164, ISSN: 1933-0219
Rhinoviruses are among the most common viruses to infect man, causing a range of serious respiratory diseases including exacerbations of asthma and COPD. Type I IFN and IL-15 are thought to be required for antiviral immunity; however, their function during rhinovirus infection in vivo is undefined. In RV-infected human volunteers, IL-15 protein expression in fluid from the nasal mucosa and in bronchial biopsies was increased. In mice, RV induced type I IFN-dependent expressions of IL-15 and IL-15Rα, which in turn were required for NK- and CD8+ T-cell responses. Treatment with IL-15–IL-15Rα complexes (IL-15c) boosted RV-induced expression of IL-15, IL-15Rα, IFN-γ, CXCL9, and CXCL10 followed by recruitment of activated, IFN-γ-expressing NK, CD8+, and CD4+ T cells. Treating infected IFNAR1−/− mice with IL-15c similarly increased IL-15, IL-15Rα, IFN-γ, and CXCL9 (but not CXCL10) expression also followed by NK-, CD8+-, and CD4+-T-cell recruitment and activation. We have demonstrated that type I IFN-induced IFN-γ and cellular immunity to RV was mediated by IL-15 and IL-15Rα. Importantly, we also show that IL-15 could be induced via a type I IFN-independent mechanism by IL-15 complex treatment, which in turn was sufficient to drive IFN-γ expression and lymphocyte responses.
Wolsk HM, Folsgaard N, Birch S, et al., 2014, The presence of viruses alters the immune signature in the airway of asymptomatic neonates, European-Academy-of-Allergy-and-Clinical-Immunology Congress, Publisher: WILEY-BLACKWELL, Pages: 192-193, ISSN: 0105-4538
Reed D, Kirkby N, Mohamed N, et al., 2014, PRINCIPAL COMPONENT ANALYSIS OF 17 CYTOKINES AND CHEMOKINES SUGGESTS THAT AUTOLOGOUS ENDOTHELIAL CELL: PBMC CO-CULTURES DELINEATE SEVERE AND MILD CYTOKINE STORM CAUSING BIOLOGICS: A NEW ASSAY FOR CYTOKINE STORM DETECTION AND RESEARCH, Publisher: WILEY-BLACKWELL, Pages: 142-143, ISSN: 1742-7835
Dhariwal J, Tennant RC, Hansell DM, et al., 2014, Smoking Cessation in COPD Causes a Transient Improvement in Spirometry and Decreases Micronodules on High-Resolution CT Imaging, CHEST, Vol: 145, Pages: 1006-1015, ISSN: 0012-3692
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- Citations: 19
Ross CL, Hansel TT, 2014, New Drug Therapies for COPD, CLINICS IN CHEST MEDICINE, Vol: 35, Pages: 219-+, ISSN: 0272-5231
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- Citations: 10
Scadding GW, Hansel TT, Durham SR, 2014, Nasal Provocation Testing, Middleton's Allergy: Principles and Practice: Eighth Edition, Pages: 652-663, ISBN: 9780323085939
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- Citations: 5
Antoniou KM, Walsh SL, Hansell DM, et al., 2013, Smoking-related emphysema is associated with idiopathic pulmonary fibrosis and rheumatoid lung, RESPIROLOGY, Vol: 18, Pages: 1191-1196, ISSN: 1323-7799
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- Citations: 41
Reed D, Gashaw H, Bailey L, et al., 2013, Use of 'same donor' endothelial cells and PBMC in co-culture to detect cytoldne storm reactions to a TGN1412-like anti-CD28 antibody: A novel assay for biologic drug safety screening, 49th Congress of the European-Societies-of-Toxicology (EUROTOX), Publisher: ELSEVIER IRELAND LTD, Pages: S164-S164, ISSN: 0378-4274
Hansel TT, Johnston SL, Openshaw PJ, 2013, Microbes and mucosal immune responses in asthma, LANCET, Vol: 381, Pages: 861-873, ISSN: 0140-6736
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- Citations: 121
Hansel T, Koehler W, Assion A, et al., 2013, Tunable Supercontinuum-Seeded 130fs OPA for NIR and MIR with 25 nJ Pulse Energy and 5 MHz Repetition Rate, Conference on Lasers and Electro-Optics (CLEO), Publisher: IEEE, ISSN: 2160-9020
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- Citations: 1
Jackson DJ, Trujillo-Torralbo M-B, Shamji B, et al., 2013, Sampling Airway Mucosal Lining Fluid Identifies Roles For Il-33 And Multiple Inflammatory Pathways In Virus-Induced Asthma Exacerbations, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 187, ISSN: 1073-449X
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Bailey L, Moreno L, Manigold T, et al., 2012, A simple whole blood bioassay detects cytokine responses to anti-CD28<sub>SA</sub> and anti-CD52 antibodies, JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, Vol: 68, Pages: 231-239, ISSN: 1056-8719
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- Citations: 11
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