Publications
121 results found
Polverino F, Longhini F, Vanaudenaerde B, et al., 2015, Juniors' voice at the ERS International Congress, Amsterdam 2015, BREATHE, Vol: 11, Pages: 303-305, ISSN: 1810-6838
Singanayagam A, Glanville N, Pearson R, et al., 2015, FLUTICASONE PROPIONATE ALTERS THE RESIDENT AIRWAY MICROBIOTA AND IMPAIRS ANTI-VIRAL AND ANTI-BACTERIAL IMMUNE RESPONSES IN THE AIRWAYS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A1-A1, ISSN: 0040-6376
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- Citations: 2
Ho W, Connell DW, Singanayagam A, et al., 2015, PREDICTIVE ACCURACY AND CLINICAL IMPACT OF XPERT MTB/RIF FOR THE DIAGNOSIS OF SPUTUM SMEAR-NEGATIVE PULMONARY TUBERCULOSIS USING BRONCHOALVEOLAR LAVAGE FLUID, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A26-A26, ISSN: 0040-6376
Ritchie AI, Farne HA, Singanayagam A, et al., 2015, Pathogenesis of Viral Infection in Exacerbations of Airway Disease., Annals of the American Thoracic Society, Vol: 12, Pages: S115-S132, ISSN: 2329-6933
Chronic airway diseases are a significant cause of morbidity and mortality worldwide, and their prevalence is predicted to increase in the future. Respiratory viruses are the most common cause of acute pulmonary infection, and there is clear evidence of their role in acute exacerbations of inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease. Studies have reported impaired host responses to virus infection in these diseases, and a better understanding of the mechanisms of these abnormal immune responses has the potential to lead to the development of novel therapeutic targets for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in acute exacerbations of chronic pulmonary diseases and to discuss exciting areas for future research and novel treatments.
Singanayagam A, Glanville N, Walton RP, et al., 2015, A short-term mouse model that reproduces the immunopathological features of rhinovirus-induced exacerbation of COPD, Clinical Science, Vol: 129, Pages: 245-258, ISSN: 1470-8736
Viral exacerbations of chronic obstructive pulmonary disease (COPD), commonly caused by rhinovirus (RV) infections, are poorly controlled by current therapies. This is due to a lack of understanding of the underlying immunopathological mechanisms. Human studies have identified a number of key immune responses that are associated with RV-induced exacerbations including neutrophilic inflammation, expression of inflammatory cytokines and deficiencies in innate anti-viral interferon. Animal models of COPD exacerbation are required to determine the contribution of these responses to disease pathogenesis. We aimed to develop a short-term mouse model that reproduced the hallmark features of RV-induced exacerbation of COPD. Evaluation of complex protocols involving multiple dose elastase and lipopolysaccharide (LPS) administration combined with RV1B infection showed suppression rather than enhancement of inflammatory parameters compared with control mice infected with RV1B alone. Therefore, these approaches did not accurately model the enhanced inflammation associated with RV infection in patients with COPD compared with healthy subjects. In contrast, a single elastase treatment followed by RV infection led to heightened airway neutrophilic and lymphocytic inflammation, increased expression of tumour necrosis factor (TNF)-α, C-X-C motif chemokine 10 (CXCL10)/IP-10 (interferon γ-induced protein 10) and CCL5 [chemokine (C-C motif) ligand 5]/RANTES (regulated on activation, normal T-cell expressed and secreted), mucus hypersecretion and preliminary evidence for increased airway hyper-responsiveness compared with mice treated with elastase or RV infection alone. In summary, we have developed a new mouse model of RV-induced COPD exacerbation that mimics many of the inflammatory features of human disease. This model, in conjunction with human models of disease, will provide an essential tool for studying disease mechanisms and allow testing of novel therapies with pot
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
Bernsmeier C, Tidswell R, Ghataore L, et al., 2015, PROOF-OF-PRINCIPLE EVALUATION OF IMMUNOMODULATORY DRUGS IN PROMOTING PHAGOCYTOSIS CAPACITY IN PATIENTS WITH LIVER FAILURE, 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver, Publisher: ELSEVIER SCIENCE BV, Pages: S324-S324, ISSN: 0168-8278
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
Singanayagam A, Glanville N, Bartlett N, et al., 2015, Effect of fluticasone propionate on virus-induced airways inflammation and anti-viral immune responses in mice, Spring Meeting on Clinician Scientists in Training, Publisher: ELSEVIER SCIENCE INC, Pages: 88-88, ISSN: 0140-6736
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- Citations: 4
Singanayagam A, Johnston SL, Mallia P, 2015, Inhaled Glucocorticoids and COPD Exacerbations, New England Journal of Medicine, Vol: 372, Pages: 92-93, ISSN: 1533-4406
Bartlett NW, Singanayagam A, Johnston SL, 2015, Mouse Models of Rhinovirus Infection and Airways Disease, RHINOVIRUSES: METHODS AND PROTOCOLS, Vol: 1221, Pages: 181-188, ISSN: 1064-3745
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- Citations: 15
Finney L, Berry M, Singanayagam A, et al., 2014, Inhaled corticosteroids and pneumonia in chronic obstructive pulmonary disease, LANCET RESPIRATORY MEDICINE, Vol: 2, Pages: 919-932, ISSN: 2213-2600
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- Citations: 55
Toussaint M, Singanayagam A, Bartlett N, et al., 2014, Rhinovirus increases allergen-induced IL-33 and exacerbates type-2 immunity and pulmonary inflammation, European-Academy-of-Allergy-and-Clinical-Immunology Congress, Publisher: WILEY-BLACKWELL, Pages: 601-601, ISSN: 0105-4538
Harrison MT, Short P, Williamson PA, et al., 2014, Thrombocytosis is associated with increased short and long term mortality after exacerbation of chronic obstructive pulmonary disease: a role for antiplatelet therapy?, THORAX, Vol: 69, Pages: 609-615, ISSN: 0040-6376
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- Citations: 77
Bernsmeier C, Patel V, Tidswell R, et al., 2014, MONOCYTE EXHAUSTION: A MECHANISTIC EXPLANATION FOR SUSCEPTIBILITY TO INFECTION IN LIVER FAILURE, 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver, Publisher: ELSEVIER SCIENCE BV, Pages: S120-S121, ISSN: 0168-8278
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- Citations: 1
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
Toussaint M, Singanayagam A, Johnston SL, et al., 2014, Role Of Interleukine-33 In Rhinovirus-Induced Allergic Asthma Exacerbation, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB52-AB52, ISSN: 0091-6749
Akram AR, Chalmers JD, Taylor JK, et al., 2013, An evaluation of clinical stability criteria to predict hospital course in community-acquired pneumonia, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 19, Pages: 1174-1180, ISSN: 1198-743X
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- Citations: 25
Taylor JK, Fleming GB, Singanayagam A, et al., 2013, Risk Factors for Aspiration in Community-acquired Pneumonia: Analysis of a Hospitalized UK Cohort, AMERICAN JOURNAL OF MEDICINE, Vol: 126, Pages: 995-1001, ISSN: 0002-9343
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- Citations: 75
Singanayagam A, Chalmers JD, 2013, Severity assessment scores to guide empirical use of antibiotics in community acquired pneumonia, LANCET RESPIRATORY MEDICINE, Vol: 1, Pages: 653-662, ISSN: 2213-2600
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- Citations: 29
Singanayagam A, Manalan K, Sridhar S, et al., 2013, Evaluation of screening methods for identification of patients with chronic rheumatological disease requiring tuberculosis chemoprophylaxis prior to commencement of TNF-α antagonist therapy, THORAX, Vol: 68, Pages: 955-961, ISSN: 0040-6376
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- Citations: 24
Singanayagam A, Glanville N, Bartlett N, et al., 2013, Development of a mouse model of COPD exacerbation, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Singanayagam A, Singanayagam A, Chalmers JD, 2013, Obesity is associated with improved survival in community-acquired pneumonia, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, Pages: 180-187, ISSN: 0903-1936
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- Citations: 65
Singanayagam A, Schembri S, Chalmers JD, 2013, Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease., Ann Am Thorac Soc, Vol: 10, Pages: 81-89
RATIONALE: There is a need to identify clinically meaningful predictors of mortality following hospitalized COPD exacerbation. OBJECTIVES: The aim of this study was to systematically review the literature to identify clinically important factors that predict mortality after hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: Eligible studies considered adults admitted to hospital with COPD exacerbation. Two authors independently abstracted data. Odds ratios were then calculated by comparing the prevalence of each predictor in survivors versus nonsurvivors. For continuous variables, mean differences were pooled by the inverse of their variance, using a random effects model. MEASUREMENTS AND MAIN RESULTS: There were 37 studies included (189,772 study subjects) with risk of death ranging from 3.6% for studies considering short-term mortality, 31.0% for long-term mortality (up to 2 yr after hospitalization), and 29.0% for studies that considered solely intensive care unit (ICU)-admitted study subjects. Twelve prognostic factors (age, male sex, low body mass index, cardiac failure, chronic renal failure, confusion, long-term oxygen therapy, lower limb edema, Global Initiative for Chronic Lung Disease criteria stage 4, cor pulmonale, acidemia, and elevated plasma troponin level) were significantly associated with increased short-term mortality. Nine prognostic factors (age, low body mass index, cardiac failure, diabetes mellitus, ischemic heart disease, malignancy, FEV1, long-term oxygen therapy, and PaO2 on admission) were significantly associated with long-term mortality. Three factors (age, low Glasgow Coma Scale score, and pH) were significantly associated with increased risk of mortality in ICU-admitted study subjects. CONCLUSION: Different factors correlate with mortality from COPD exacerbation in the short term, long term, and after ICU admission. These parameters may be useful to develop tools for prediction of outcome
Schembri S, Williamson PA, Short PM, et al., 2013, Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies, BMJ-BRITISH MEDICAL JOURNAL, Vol: 346, ISSN: 1756-1833
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- Citations: 85
Huang J, Kumar S, Singanayagam A, et al., 2013, Exhaled breath acetone for therapeutic monitoring in pneumonia using selected ion flow tube mass spectrometry (SIFT-MS), ANALYTICAL METHODS, Vol: 5, Pages: 3807-3810, ISSN: 1759-9660
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- Citations: 11
Mallia P, Singanayagam A, Johnston SL, 2013, Virus-bacteria interactions in COPD exacerbations, SPECTRUM OF BRONCHIAL INFECTION, Pages: 76-83, ISSN: 2075-6674
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- Citations: 3
Singanayagam A, Short PM, Archibald R, et al., 2013, Effect Of Antibiotic Use On Short And Long Term Outcome In Hospitalized Chronic Obstructive Pulmonary Disease (COPD) Exacerbations, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Singanayagam A, Short P, Williamson P, et al., 2012, CARDIOVASCULAR EVENTS FOLLOWING CLARITHROMYCIN USE IN LOWER RESPIRATORY TRACT INFECTIONS: ANALYSIS OF TWO PROSPECTIVE COHORT STUDIES, Winter Meeting of the British-Thoracic-Society 2012, Publisher: BMJ PUBLISHING GROUP, Pages: A15-A16, ISSN: 0040-6376
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- Citations: 1
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