Publications
381 results found
Jha A, Kon OM, 2015, Overview of pulmonary, pleural and mediastinal investigations in active tuberculosis, Minerva Pneumologica, Vol: 54, Pages: 85-101, ISSN: 0026-4954
Tuberculosis (TB) in Europe remains an important source of morbidity and with a notification rate of up to 85 per 100,000 of the population in some European Union (EU) countries, the need for accurate and earlydiagnosis is crucial. Spontaneous sputum sampling for obtaining cultures remains the commonest method for diagnosing pulmonarytuberculosis, whilst the introduction of the Gene Xpert MTB/RIF test may offer a more rapid and sensitive option to the traditional smear due to its ability to simultaneously diagnose Mycobacterium tuberculosisand identify Rifampicin resistant strains with great accuracy. Standard and high resolution computed tomography (HRCT), as well as positron emission tomography (PET) scanning are becoming important tools forsmear negative cases or those with complex presentations. The difficulties of diagnosing pleural TB have been improved with theadvent of specific and non-specific immune markers such as adenosine deaminase (ADA) and interferon gamma (IFN-γ), as well as by the ability to obtain highly accurate biopsies with thoracoscopy. Mediastinal and hilar lymphadenitis is a common presentationof the disease and endobronchial ultrasound with transbronchial needle aspiration (EBUSTBNA) is a safe and highly sensitive procedurewhich is rapidly establishing itself as a first line tool in the diagnosis of intrathoracic TB. In this review we outline the host and environmental factors that contribute to the propagation of pulmonary tuberculosis.
Hewitt RJ, Singanayagam A, Sridhar S, et al., 2015, Screening for latent tuberculosis before tumour necrosis factor antagonist therapy, EUROPEAN RESPIRATORY JOURNAL, Vol: 45, Pages: 1510-1512, ISSN: 0903-1936
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- Citations: 2
Pollock KM, Montamat-Sicotte DJ, Cooke GS, et al., 2015, Differences in antigen-specific CD4+ responses to opportunistic infections in HIV infection, Immunity, Inflammation and Disease, Vol: 3, Pages: 141-153, ISSN: 2050-4527
HIV-infected individuals with severe immunodeficiency are at risk of opportunistic infection (OI). Tuberculosis (TB) may occur without substantial immune suppression suggesting an early and sustained adverse impact of HIV on Mycobacterium tuberculosis (MTB)-specific cell mediated immunity (CMI). This prospective observational cohort study aimed to observe differences in OI-specific and MTB-specific CMI that might underlie this. Using polychromatic flow cytometry, we compared CD4+ responses to MTB, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Candida albicans in individuals with and without HIV infection. MTB-specific CD4+ T-cells were more polyfunctional than virus specific (CMV/EBV) CD4+ T-cells which predominantly secreted IFN-gamma (IFN-γ) only. There was a reduced frequency of IFN-γ and IL-2 (IL-2)-dual-MTB-specific cells in HIV-infected individuals, which was not apparent for the other pathogens. MTB-specific cells were less differentiated especially compared with CMV-specific cells. CD127 expression was relatively less frequent on MTB-specific cells in HIV co-infection. MTB-specific CD4+ T-cells PD-1 expression was infrequent in contrast to EBV-specific CD4+ T-cells. The variation in the inherent quality of these CD4+ T-cell responses and impact of HIV co-infection may contribute to the timing of co-infectious diseases in HIV infection.
Kon OM, 2015, SCREENING TESTS FOR TB BEFORE BIOLOGICAL THERAPY Author's reply to Clifford and colleagues, BMJ-BRITISH MEDICAL JOURNAL, Vol: 350, ISSN: 0959-535X
Manalan K, Singanayagam A, Wickremasinghe M, et al., 2015, Letter in response to TB during TNF-α inhibitor therapy, despite screening., Thorax, Vol: 70
Manalan K, Singanayagam A, Wickremasinghe M, et al., 2015, Letter in response to TB during TNF-α inhibitor therapy, despite screening, THORAX, Vol: 70, Pages: 373-373, ISSN: 0040-6376
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- Citations: 1
Hewitt RJ, Francis M, Singanayagam A, et al., 2015, RATIONAL TESTING Screening tests for tuberculosis before starting biological therapy, BMJ-BRITISH MEDICAL JOURNAL, Vol: 350, ISSN: 0959-535X
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- Citations: 10
Kon OM, Ormerod LP, 2015, The national TB strategy: jointly taking responsibility for TB control?, THORAX, Vol: 70, Pages: 211-212, ISSN: 0040-6376
Potter JL, Capstick T, Ricketts WM, et al., 2015, A UK-based resource to support the monitoring and safe use of anti-TB drugs and second-line treatment of multidrug-resistant TB, THORAX, Vol: 70, Pages: 297-298, ISSN: 0040-6376
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- Citations: 7
Boshier PR, Mistry V, Cushnir JR, et al., 2015, Breath metabolite response to major upper gastrointestinal surgery, JOURNAL OF SURGICAL RESEARCH, Vol: 193, Pages: 704-712, ISSN: 0022-4804
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- Citations: 4
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
Starren E, Oldfield WL, Kon OM, 2015, Pulmonary insufficiency, ESSENTIAL SURGICAL PRACTICE: HIGHER SURGICAL TRAINING IN GENERAL SURGERY, 5TH EDITION, Editors: Cuschieri, Hanna, Publisher: CRC PRESS-TAYLOR & FRANCIS GROUP, Pages: 182-188, ISBN: 978-1-4441-3762-0
Kow KJH, Connell DW, Singanayagam A, et al., 2014, INTRATHORACIC LYMPH NODE TUBERCULOSIS - A COMPREHENSIVE CLINICAL DESCRIPTION, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A157-A158, ISSN: 0040-6376
Jozwik A, Habibi M, Paras A, et al., 2014, Human T-cell responses to RSV infection in the lower airway, IMMUNOLOGY, Vol: 143, Pages: 76-76, ISSN: 0019-2805
Jackson DJ, Makrinioti H, Rana BMJ, et al., 2014, IL-33-dependent Type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo, American Journal of Respiratory and Critical Care Medicine, Vol: 190, Pages: 1373-1382, ISSN: 1535-4970
Rationale: Rhinoviruses are the major cause of asthmaexacerbations; however, its underlying mechanisms are poorlyunderstood. We hypothesized that the epithelial cell–derivedcytokine IL-33 plays a central role in exacerbation pathogenesisthrough augmentation of type 2 inflammation.Objectives: To assess whether rhinovirus induces a type 2inflammatory response in asthma in vivo and to define a role for IL-33in this pathway.Methods: We used a human experimental model of rhinovirusinfection and novel airway sampling techniques to measure IL-4, IL-5,IL-13, and IL-33 levels in the asthmatic and healthy airways duringa rhinovirus infection. Additionally, we cultured human T cells and type2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirusinfectedbronchial epithelial cells (BECs) to assess type 2 cytokineproduction in the presence or absence of IL-33 receptor blockade.Measurements and Main Results: IL-4, IL-5, IL-13, and IL-33 areall induced by rhinovirus in the asthmatic airway in vivo and relate toexacerbation severity. Further, induction of IL-33 correlates withviral load and IL-5 and IL-13 levels. Rhinovirus infection of humanprimary BECs induced IL-33, and culture of human T cells and ILC2swith supernatants of rhinovirus-infected BECs strongly inducedtype 2 cytokines. This induction was entirely dependent on IL-33.Conclusions: IL-33 and type 2 cytokines are induced duringa rhinovirus-induced asthma exacerbation in vivo. Virus-inducedIL-33 and IL-33–responsive T cells and ILC2s are key mechanisticlinks between viral infection and exacerbation of asthma. IL-33inhibition is a novel therapeutic approach for asthma exacerbations
Singanayagam A, Donaldson H, Kon OM, 2014, GeneXpert® MTB/RIF in low prevalence settings: A UK laboratory perspective, JOURNAL OF INFECTION, Vol: 69, Pages: 199-200, ISSN: 0163-4453
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- Citations: 2
Rohde G, Message SD, Haas JJ, et al., 2014, CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental asthma exacerbations, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 44, Pages: 930-939, ISSN: 0954-7894
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- Citations: 42
Zhu J, Message SD, Qiu Y, et al., 2014, Airway Inflammation and Illness Severity in Response to Experimental Rhinovirus Infection in Asthma, Chest, Vol: 145, Pages: 1219-1229, ISSN: 0012-3692
BackgroundThe nature of bronchial mucosal inflammation and its physiologic and clinical significance in rhinovirus-induced asthma exacerbations is unclear. We investigated bronchial mucosal inflammatory response and its association with physiologic and clinical outcomes in an experimental model of rhinovirus-induced asthma exacerbations.MethodsWe used immunohistochemistry methods to detect phenotypes of inflammatory cells infiltrating the bronchial mucosa before and after experimental rhinovirus infection in 10 subjects with asthma and 15 normal subjects.ResultsCompared with baseline, rhinovirus infection significantly increased the number of epithelial (P = .005) and subepithelial (P = .017) neutrophils in subjects with asthma only and subepithelial CD68+ macrophages in both subjects with asthma (P = .009) and normal subjects (P = .018) but more so in those with asthma (P = .021). Numbers of CD45+, CD68+, and CD20+ cells; neutrophils; and eosinophils at day 4 postinfection were positively associated with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects with asthma, CD4+ cells correlated with chest symptom scores (r = 0.69, P = .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = −0.89, P = .029), the PC10 correlated inversely with CD4+ (r = −0.67, P = .023) and CD8+ cells (r = −0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = −0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = −0.72, P = .03), whereas higher subepithelial mast cell counts were significantly associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P = .024).ConclusionsIn subjects with asthma, rhinovirus infection induces bronchial mucosal neutrophilia and more severe monocyte/macrophage infiltration than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes during in
Hingley-Wilson SM, Connell D, Pollock K, et al., 2014, ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans, TUBERCULOSIS, Vol: 94, Pages: 262-270, ISSN: 1472-9792
Mycobacterium tuberculosis-induced cellular aggregation is essential for granuloma formation and may assist establishment and early spread of M. tuberculosis infection. The M. tuberculosis ESX1 mutant, which has a non-functional type VII secretion system, induced significantly less production of the host macrophage-derived chemokine fractalkine (CX3CL1). Upon infection of human macrophages ESX1-dependent fractalkine production mediated selective recruitment of CD11b+ monocytic cells and increased infection of neighbouring cells consistent with early local spread of infection. Fractalkine levels were raised in vivo at tuberculous disease sites in humans and were significantly associated with increased CD11b+ monocytic cellular recruitment and extent of granulomatous disease. These findings suggest a novel fractalkine-dependent ESX1-mediated mechanism in early tuberculous disease pathogenesis in humans. Modulation of M. tuberculosis-mediated fractalkine induction may represent a potential treatment option in the future, perhaps allowing us to switch off a key mechanism required by the pathogen to spread between cells.
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
Kon OM, 2014, Time for a preventative strategy for TB in the UK: further evidence for new entrant screening in primary care, THORAX, Vol: 69, Pages: 305-306, ISSN: 0040-6376
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- Citations: 3
Sykes A, Macintyre J, Edwards MR, et al., 2014, Rhinovirus-induced interferon production is not deficient in well controlled asthma, THORAX, Vol: 69, Pages: 240-246, ISSN: 0040-6376
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- Citations: 109
Dhasmana DJ, Ross C, Bradley C, et al., 2014, Performance of Xpert MTB/RIF in the diagnosis of tuberculous mediastinal lymphadenopathy by endobronchial ultrasound., Annals of the American Thoracic Society, Vol: 11, Pages: 392-396, ISSN: 2329-6933
RATIONALE: The Xpert (GeneXpert) MTB/RIF, an integrated polymerase chain reaction assay, has not been systematically studied in extrapulmonary and in particular mediastinal tuberculosis (TB). OBJECTIVES: To investigate the performance of Xpert MTB/RIF in the diagnosis of intrathoracic nodal TB in a large tertiary urban medical center in the UK. METHODS: We collected clinical, cytological, and microbiological data from two cohorts: 116 consecutive patients referred with mediastinal lymphadenopathy with detailed diagnostic information obtained, and an immediately subsequent second cohort of 52 consecutive patients with microbiologically confirmed mediastinal TB lymphadenopathy. All data were derived between January 2010 and October 2012. All patients underwent endobronchial ultrasound and transbronchial needle aspiration (TBNA). The performance of a single Xpert MTB/RIF assay alongside standard investigations, cytology, and microscopy/culture was evaluated against culture-confirmed TB. MEASUREMENTS AND MAIN RESULTS: Microbiologically confirmed TB mediastinal lymphadenopathy was diagnosed in a total of 88 patients from both cohorts. Three culture-negative cases with associated caseating granulomatous inflammation on TBNA were given a probable diagnosis. A single Xpert MTB/RIF assay demonstrated overall sensitivity for culture-positive TB of 72.6% (62.3-81.0%). Xpert specificity from cohort 1 was 96.3% (89.1-99.1%). The positive predictive value was 88.9% (69.7-97.1%), negative predictive value was 86.5% (76.9-92.1%), and odds ratio was 51.3 (24.0-98.0) for correctly identifying culture-positive disease. Xpert captured all microscopy-positive cases (14 of 14) and the majority of microscopy-negative cases (48 of 71, 67.6%). Among the cases that were culture positive by TBNA, Xpert identified two-thirds of the multiple drug-resistant TB cases, leading to immediate regimen change up to 5 weeks ahead of positive cultures. The use of Xpert combined with cytology increased th
Mallia P, Message SD, Contoli M, et al., 2014, Lymphocyte subsets in experimental rhinovirus infection in chronic obstructive pulmonary disease, Respiratory Medicine, Vol: 108, Pages: 78-85, ISSN: 0954-6111
BackgroundCOPD is associated with increased numbers of T cells in the lungs, particularly CD8+ T cells. The mechanisms of increased T cells are unknown but may be related to repeated virus infections in COPD patients. We analysed lymphocyte subsets in blood and bronchoalveolar lavage in smokers and COPD subjects during experimental rhinovirus infections.MethodsLymphocytes were isolated from blood and bronchoalveolar lavage from COPD subjects and non-obstructed smokers prior to, and following experimental rhinovirus infection. Lymphocyte surface markers and intracellular cytokines were analysed using flow cytometry.ResultsFollowing rhinovirus infection CD4+ and CD8+ T cell numbers in the COPD subjects were significantly reduced in blood and CD3+ and CD8+ T cells increased in bronchoalveolar lavage compared to baseline. T cells did not increase in BAL in the control subjects. CD3+ T cells correlated with virus load.ConclusionsFollowing rhinovirus infection T cells move from the circulation to the lung. Repeated virus infections may contribute to T cell accumulation in COPD patients.
Anwar MS, Kow K, Grass L, et al., 2014, Utility Of Interferon-γ Release Assays In Combination With Tuberculin Skin Tests In Active Tb, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 189, ISSN: 1073-449X
Ross CL, Anwar M, Wickremasinghe M, et al., 2013, SENSITIVITY OF THE XPERT® MTB/RIF ASSAY IN BRONCHOALVEOLAR LAVAGE SAMPLES IN A NORTH WEST LONDON HOSPITAL: A USEFUL ADJUNCT TO CURRENT DIAGNOSTIC MODALITIES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A85-A85, ISSN: 0040-6376
Keal JL, Capstick TG, Ricketts WM, et al., 2013, MULTI-DRUG RESISTANT TUBERCULOSIS: THE FIRST UK GUIDELINE FOR TREATMENT MONITORING, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A119-A119, ISSN: 0040-6376
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- Citations: 1
Footitt J, Mallia P, Durham A, et al., 2013, HDAC ACTIVITY IN MACROPHAGES IN EXPERIMENTAL RHINOVIRUS INFECTION IN COPD, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A58-A59, ISSN: 0040-6376
Molyneaux PL, Mallia P, Cox MJ, et al., 2013, Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 188, Pages: 1224-1231, ISSN: 1073-449X
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- Citations: 262
Glanville N, Message SD, Walton RP, et al., 2013, γδT cells suppress inflammation and disease during rhinovirus-induced asthma exacerbations, Mucosal Immunology, Vol: 6, Pages: 1091-1100, ISSN: 1933-0219
Most asthma exacerbations are triggered by virus infections, the majority being caused by human rhinoviruses (RV). In mouse models, γδT cells have been previously demonstrated to influence allergen-driven airways hyper-reactivity (AHR) and can have antiviral activity, implicating them as prime candidates in the pathogenesis of asthma exacerbations. To explore this, we have used human and mouse models of experimental RV-induced asthma exacerbations to examine γδT-cell responses and determine their role in the immune response and associated airways disease. In humans, airway γδT-cell numbers were increased in asthmatic vs. healthy control subjects during experimental infection. Airway and blood γδT-cell numbers were associated with increased airways obstruction and AHR. Airway γδT-cell number was also positively correlated with bronchoalveolar lavage (BAL) virus load and BAL eosinophils and lymphocytes during RV infection. Consistent with our observations of RV-induced asthma exacerbations in humans, infection of mice with allergic airways inflammation increased lung γδT-cell number and activation. Inhibiting γδT-cell responses using anti-γδTCR (anti-γδT-cell receptor) antibody treatment in the mouse asthma exacerbation model increased AHR and airway T helper type 2 cell recruitment and eosinophilia, providing evidence that γδT cells are negative regulators of airways inflammation and disease in RV-induced asthma exacerbations.
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