302 results found
Agrawal R, Betzler BK, Testi I, et al., 2020, The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 447 Patients with Tubercular Intermediate Uveitis and Panuveitis., Ocul Immunol Inflamm, Pages: 1-11
Purpose: Tubercular intermediate uveitis (TIU) and panuveitis (TBP) are difficult to manage because of limitations in diagnostic tools and lack of evidence-based treatment guidelines. The Collaborative Ocular Tuberculosis Study (COTS) analyzed treatment regimens and therapeutic outcomes in patients with TIU and TBP. Methods: Multicentre retrospective analysis. Results A total of 138 TIU and 309 TBP patients were included. A total of 382 subjects received antitubercular therapy (ATT) (n = 382/447; 85.4%) and 382 received corticosteroids (n = 382/447; 85.4%). Treatment failure was observed in 78 individuals (n = 78/447; 17.4%), occurring less frequently in patients receiving ATT (n = 66/382; 17.2%) compared to those who did not (n = 12/65; 18.5%). The study did not show any statistically significant therapeutic effect of ATT in patients with TIU and TBP. Conclusion Taking into account the limitations of the retrospective, non-randomized study design, resultant reliance on reported data records, and unequal size of the samples, the current study cannot provide conclusive evidence on the therapeutic benefit of ATT in TIU and TBP.
Dhawan RT, Gopalan D, Howard L, et al., 2020, Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19., Lancet Respir Med
A compelling body of evidence points to pulmonary thrombosis and thromboembolism as a key feature of COVID-19. As the pandemic spread across the globe over the past few months, a timely call to arms was issued by a team of clinicians to consider the prospect of long-lasting pulmonary fibrotic damage and plan for structured follow-up. However, the component of post-thrombotic sequelae has been less widely considered. Although the long-term outcomes of COVID-19 are not known, should pulmonary vascular sequelae prove to be clinically significant, these have the potential to become a public health problem. In this Personal View, we propose a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential haemodynamic sequelae. A nuanced and physiological approach to follow-up imaging that looks beyond the clot, at the state of perfusion of lung tissue, is proposed as a key triage tool, with the potential to inform therapeutic strategies.
Zhu J, Mallia P, Footitt J, et al., 2020, Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD, Journal of Allergy and Clinical Immunology, Vol: 146, Pages: 840-850.e7, ISSN: 0091-6749
BackgroundRespiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity.ObjectivesWe sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16–induced COPD exacerbations and its relationship to disease severity.MethodsBronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests.ResultsRV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4+ T lymphocytes, and CD20+ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T lymphocytes but fewer numbers of CD4+ T lymphocytes and CD20+ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function.ConclusionsExperimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflamma
Harlow CF, Meghji J, Martin L, et al., 2020, Republished: Rifampicin induced shock during re-exposure for treatment of latent tuberculosis., Drug Ther Bull, Vol: 58, Pages: 157-159
Park M, Kon OM, 2020, Use of Xpert MTB/RIF and Xpert Ultra in extrapulmonary tuberculosis, EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, ISSN: 1478-7210
Park M, Owles H, Williams A, et al., 2020, PEDIATRIC ENDOBRONCHIAL ULTRASOUNDTRANSBRONCHIALNEEDLE ASPIRATION UNDERCONSCIOUS SEDATION FOR SUSPECTEDTUBERCULOSIS IN LONDON, Paediatric infectious diseases journal
Testi I, Agrawal R, Mahajan S, et al., 2020, The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Descriptive Review of Tubercular Uveitis in Paediatric Population, OCULAR IMMUNOLOGY AND INFLAMMATION, ISSN: 0927-3948
Jha A, Thwaites RS, Tunstall T, et al., 2020, Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis., J Allergy Clin Immunol
BACKGROUND: Acute respiratory viral infections are a major cause of respiratory morbidity and mortality, especially in patients with preexisting lung diseases such as asthma. Toll-like receptors are critical in the early detection of viruses and in activating innate immunity in the respiratory mucosa, but there is no reliable and convenient method by which respiratory mucosal innate immune responses can be measured. OBJECTIVE: We sought to assess in vivo immune responses to an innate stimulus and compare responsiveness between healthy volunteers and volunteers with allergy. METHODS: We administered the Toll-like receptor 7/8 agonist resiquimod (R848; a synthetic analogue of single-stranded RNA) or saline by nasal spray to healthy participants without allergy (n = 12), those with allergic rhinitis (n = 12), or those with allergic rhinitis with asthma (n = 11). Immune mediators in blood and nasal fluid and mucosal gene expression were monitored over time. RESULTS: R848 was well tolerated and significantly induced IFN-α2a, IFN-γ, proinflammatory cytokines (TNF-α, IL-2, IL-12p70), and chemokines (CXCL10, C-C motif chemokine ligand [CCL]2, CCL3, CCL4, and CCL13) in nasal mucosal fluid, without causing systemic immune activation. Participants with allergic rhinitis or allergic rhinitis with asthma had increased IFN-α2a, CCL3, and CCL13 responses relative to healthy participants; those with asthma had increased induction of IFN-stimulated genes DExD/H-box helicase 58, MX dynamin-like GTPase 1, and IFN-induced protein with tetratricopeptide repeats 3. CONCLUSIONS: Responses to nasal delivery of R848 enables simple assessment of mucosal innate responsiveness, revealing that patients with allergic disorders have an increased nasal mucosal IFN and chemokine response to the viral RNA analogue R848. This highlights that dysregulated innate immune responses of the nasal mucosa in allergic individuals may be important in determining the
Agarwal A, Agrawal R, Raje D, et al., 2020, Twenty-four Month Outcomes in the Collaborative Ocular Tuberculosis Study (COTS)-1: Defining the "Cure" in Ocular Tuberculosis, OCULAR IMMUNOLOGY AND INFLAMMATION, ISSN: 0927-3948
Agrawal R, Betzler B, Testi I, et al., 2020, The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 165 Patients with Tubercular Anterior Uveitis, OCULAR IMMUNOLOGY AND INFLAMMATION, ISSN: 0927-3948
Agrawal R, Gunasekeran DV, Agarwal A, et al., 2020, Visual Morbidity in Ocular Tuberculosis - Collaborative Ocular Tuberculosis Study (COTS)-1: Report #6, OCULAR IMMUNOLOGY AND INFLAMMATION, ISSN: 0927-3948
Agrawal R, Testi I, Bodaghi B, et al., 2020, Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis., Ophthalmology
TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS
Chua F, Armstrong-James D, Desai SR, et al., 2020, The role of CT in case ascertainment and management of COVID-19 pneumonia in the UK: insights from high-incidence regions, LANCET RESPIRATORY MEDICINE, Vol: 8, Pages: 438-440, ISSN: 2213-2600
Petrushkin H, Sethi C, Potter J, et al., 2020, Developing a pathway for the diagnosis and management of ocular tuberculosis. The pan-LOndon Ocular tuberculosis Pathway-LOOP, EYE, Vol: 34, Pages: 805-808, ISSN: 0950-222X
Agrawal R, Testi I, Mahajan S, et al., 2020, The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings, OCULAR IMMUNOLOGY AND INFLAMMATION, ISSN: 0927-3948
Testi I, Betzler B, Gupta V, et al., 2020, Current clinical management of ocular tuberculosis, EXPERT REVIEW OF OPHTHALMOLOGY, Vol: 15, Pages: 93-99, ISSN: 1746-9899
Tiberi S, Zumla A, Raviglione M, et al., 2020, A postgraduate qualification in tuberculosis-Message in a bottle, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 92, Pages: S100-S102, ISSN: 1201-9712
Harlow CF, Meghji J, Martin L, et al., 2020, Rifampicin induced shock during re-exposure for treatment of latent tuberculosis., BMJ Case Rep, Vol: 13
We present a case of a young Asian female with rheumatoid arthritis who received latent tuberculosis infection (LTBI) treatment prior to treatment with a biologic agent, and developed shock with resistant hypotension on re-exposure to rifampicin. We discuss the epidemiology, pathophysiology and management of rifampicin induced shock, concluding that clinicians should be aware of this rare, but potential adverse effect, and be aware that adverse reactions to rifampicin are more frequent during re-exposure or longer dosing interval regimes. The evidence for desensitisation following such a reaction is lacking and this approach is not currently recommended. We would suggest close collaboration between specialties prescribing immunosuppression and the tuberculosis team when LTBI treatment is required after a reaction, with patient involvement to discuss the risks and benefits of treatment options.
Agrawal R, Testi I, Mahajan S, et al., 2020, Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis., Ophthalmology
TOPIC: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. CLINICAL RELEVANCE: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. METHODS: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. RESULTS: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were consider
Guvenel A, Jozwik A, Ascough S, et al., 2020, Epitope-specific airway-resident CD4+ T-cell dynamics during experimental human RSV infection, Journal of Clinical Investigation, Vol: 130, Pages: 523-538, ISSN: 0021-9738
Background: Respiratory syncytial virus (RSV) is an important cause of acute pulmonary disease and one of the last remaining major infections of childhood for which there is no vaccine. CD4+ T-cells play a key role in antiviral immunity, but they have been little studied in the human lung. Methods: Healthy adult volunteers were inoculated intranasally with RSV A Memphis 37. CD4+ T-cells in blood and lower airway were analysed by flow cytometry and immunohistochemistry. Bronchial soluble mediators were measured using quantitative PCR and MesoScale Discovery. Epitope mapping was performed by IFN-γ ELISpot screening, confirmed by in vitro MHC binding. Results: Activated CD4+ T-cell frequencies in bronchoalveolar lavage correlated strongly with local CXCL10 levels. Thirty-nine epitopes were identified, predominantly towards the 3’ end of the viral genome. Five novel MHC-II tetramers were made using an immunodominant F-EFY epitope restricted to HLA-DR4, -DR9 and -DR11 (combined allelic frequency: 15% in Europeans) and G- DDF restricted to HLA-DPA1*01:03/DPB1*02:01 and -DPA1*01:03/DPB1*04:01 (allelic frequency: 55%). Tetramer labelling revealed enrichment of resident memory CD4+ T-cells (TRM) cells in the lower airway; these TRM displayed progressive differentiation, down-regulation of co- stimulatory molecules and elevated CXCR3 expression as infection evolved. Conclusion: Human infection challenge provides a unique opportunity to study the breadth of specificity and dynamics of RSV-specific T-cell responses in the target organ, allowing the precise investigation of TRM recognising novel viral antigens over time. The new tools that we describe enable precise tracking of RSV-specific CD4+ cells, potentially accelerating the development of effective vaccines.
Manalan K, Green N, Arnold A, et al., 2020, A cost comparison of amikacin therapy with bedaquiline, for drug-resistant tuberculosis in the UK, JOURNAL OF INFECTION, Vol: 80, Pages: 38-41, ISSN: 0163-4453
Farne H, Glanville N, Johnson N, et al., 2020, The CRTH2 Antagonist Timapiprant Does Not Alter the Response Rhinovirus Infection in Asthma: A Randomized, Placebo-Controlled Trial, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Agrawal R, Agarwal A, Jabs DA, et al., 2019, Standardization of nomenclature for ocular tuberculosis - results of Collaborative Ocular Tuberculosis Study (COTS) workshop, Ocular Immunology and Inflammation, ISSN: 0927-3948
Purpose: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).Methods: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.Results: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease “remission” and “cure”, both of which are relevant for reporting treatment outcomes.Conclusion: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity.
Park M, Dave D, Russell G, et al., 2019, FDG-PET/CT APPEARANCES IN MDR-TB PATIENTS WITH RESIDUAL CT ABNORMALITIES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A69-A70, ISSN: 0040-6376
Park M, Satta G, Coleman M, et al., 2019, DIAGNOSTIC ACCURACY OF XPERT ULTRA FOR THE DETECTION OF MTB IN BRONCHOALVEOLAR LAVAGE SAMPLES FOR PULMONARY TUBERCULOSIS IN A TERTIARY TB CENTRE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A70-A70, ISSN: 0040-6376
Testi I, Agrawal R, Mahajan S, et al., 2019, Tubercular Uveitis: Nuggets from Collaborative Ocular Tuberculosis Study (COTS)-1, OCULAR IMMUNOLOGY AND INFLAMMATION, ISSN: 0927-3948
Berrocal-Almanza LC, Harris R, Lalor MK, et al., 2019, Effectiveness of pre-entry active tuberculosis and post-entry latent tuberculosis screening in new entrants to the UK: a retrospective, population-based cohort study., Lancet Infectious Diseases, Vol: 19, Pages: 1191-1201, ISSN: 1473-3099
BACKGROUND: Evaluating interventions that might lead to a reduction in tuberculosis in high-income countries with a low incidence of the disease is key to accelerate progress towards its elimination. In such countries, migrants are known to contribute a large proportion of tuberculosis cases to the burden. We assessed the effectiveness of screening for active tuberculosis before entry to the UK and for latent tuberculosis infection (LTBI) post-entry for reduction of tuberculosis in new-entrant migrants to the UK. Additionally, we investigated the effect of access to primary care on tuberculosis incidence in this population. METHODS: We did a retrospective, population-based cohort study of migrants from 66 countries who were negative for active tuberculosis at pre-entry screening between Jan 1, 2011, and Dec 31, 2014, and eligible for LTBI screening. We used record linkage to track their first contact with primary care, uptake of LTBI screening, and development of active tuberculosis in England, Wales, and Northern Ireland. To assess the effectiveness of the pre-entry screening programme, we identified a control group of migrants who were not screened for active tuberculosis using the specific code for new entrants to the UK registering in primary care within the National Health Service patient registration data system. Our primary outcome was development of active tuberculosis notified to the National Enhanced Tuberculosis Surveillance System. FINDINGS: Our cohort comprised 224 234 migrants who were screened for active tuberculosis before entry to the UK and a control group of 118 738 migrants who were not. 103 990 (50%) migrants who were screened for active tuberculosis registered in primary care; all individuals in the control group were registered in primary care. 1828 tuberculosis cases were identified during the cohort time, of which 31 were prevalent. There were 26 incident active tuberculosis cases in migrants with no evidence of primary care registration, an
Jha A, Dunning J, Tunstall T, et al., 2019, Patterns of systemic and local inflammation in patients with asthma hospitalised with influenza, European Respiratory Journal, Vol: 54, ISSN: 0903-1936
BackgroundPatients with asthma are at risk of hospitalisation with influenza, but the reasons for this predisposition are unknown.Study settingA prospective observational study of adults with PCR-confirmed influenza in 11 UK hospitals, measuring nasal, nasopharyngeal and systemic immune mediators and whole-blood gene expression.ResultsOf 133 admissions, 40 (30%) had previous asthma; these were more often female (70% vs 38.7%, OR 3.69, 95% CI 1.67 to 8.18, P = 0.0012), required less mechanical ventilation (15% vs 37.6%, χ2 6.78, P=0.0338) and had shorter hospital stays (mean 8.3 vs 15.3 d, P=0.0333) than those without. In patients without asthma, severe outcomes were more frequent in those given corticosteroids (OR=2.63, 95% CI=1.02-6.96, P=0.0466) or presenting >4 days after disease onset (OR 5.49, 95% CI 2.28–14.03, P=0.0002). Influenza vaccination in at-risk groups (including asthma) were lower than intended by national policy and the early use of antiviral medications were less than optimal. Mucosal immune responses were equivalent between groups. Those with asthma had higher serum IFN-α but lower serum TNF, IL-5, IL-6, CXCL8, CXCL9, IL-10, IL-17 and CCL2 levels (all P<0.05); both groups had similar serum IL-13, total IgE, periostin and blood eosinophil gene expression levels. Asthma diagnosis was unrelated to viral load, IFN-α, IFN-γ, IL-5 or IL-13 levels.ConclusionsAsthma is common in those hospitalised with influenza, but may not represent classical Type 2-driven disease. Those admitted with influenza tend to be female with mild serum inflammatory responses, increased serum IFN-α levels and good clinical outcomes.
Abbara A, Collin SM, Kon OM, et al., 2019, Time to diagnosis of tuberculosis is greater in older patients: a retrospective cohort review, ERJ OPEN RESEARCH, Vol: 5
Stagg HR, Bothamley GH, Davidson JA, et al., 2019, Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance, EUROPEAN RESPIRATORY JOURNAL, Vol: 54, ISSN: 0903-1936
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