Imperial College London

Dr Onn Min Kon

Faculty of MedicineNational Heart & Lung Institute

Professor of Respiratory Medicine
 
 
 
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Contact

 

+44 (0)20 3312 1751onn.kon CV

 
 
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Location

 

Mint WingSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

380 results found

Agrawal RV, Betzler B, Putera I, Nora RLD, Testi I, Kon OM, Kempen JH, Pavesio C, Gupta Vet al., 2022, Anti-Tubercular Therapy in the Treatment of Tubercular Uveitis, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Halliday A, Masonou T, Tolosa-Wright MR, Guo Y, Hoang L, Parker R, Boakye A, Takwoingi Y, Badhan A, Jain P, Marwah I, Berrocal-Almanza LC, Deeks J, Beverley P, Kon OM, Lalvani Aet al., 2022, Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis, Journal of Infectious Diseases, Vol: 225, Pages: 1632-1641, ISSN: 0022-1899

BACKGROUND: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown. METHODS: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry. RESULTS: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects. CONCLUSIONS: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB.

Journal article

Cohen JM, Banks M, Kon OM, Eisen Set al., 2022, UTILITY OF ESOPHAGEAL ULTRASOUND-GUIDED BIOPSY OF MEDIASTINAL LYMPH NODES IN DIAGNOSIS OF CHILDHOOD TUBERCULOSIS, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 41, Pages: E246-E248, ISSN: 0891-3668

Journal article

Park M, Lalvani A, Satta G, Kon OMet al., 2022, Evaluating the clinical impact of routine whole genome sequencing in tuberculosis treatment decisions and the issue of isoniazid mono-resistance, BMC Infectious Diseases, Vol: 22, Pages: 1-10, ISSN: 1471-2334

BackgroundThe UK has implemented routine use of whole genome sequencing (WGS) in TB diagnostics. The WHO recommends addition of a fluoroquinolone for isoniazid mono-resistance, so early detection may be of use. The aim of this study was to describe the clinical utility and impact of WGS on treatment decisions for TB in a low incidence high resource clinical setting. The clinical turnaround time (TAT) for WGS was analysed in comparison to TB PCR using Xpert MTB/RIF (Cepheid, Sunnyvale, CA) results where available and subsequent phenotypic drug susceptibility testing (DST) when required.MethodsThis was a retrospective analysis of TB cases from January 2018 to March 2019 in London. Susceptibility and TAT by WGS, phenotypic DST, TB PCR using Xpert MTB/RIF were correlated to drug changes in order to describe the utility of WGS on treatment decisions on isoniazid mono-resistance in a low incidence high resource setting.Results189 TB cases were identified; median age 44 years (IQR 28–60), m:f ratio 112:77, 7 with HIV and 6 with previous TB. 80/189 cases had a positive culture and WGS result. 50/80 were fully sensitive to 1st line treatment on WGS, and the rest required additional DST. 20/80 cases required drug changes; 12 were defined by WGS: 8 cases had isoniazid mono-resistance, 2 had MDR-TB, 1 had isoniazid and pyrazinamide resistance and 1 had ethambutol resistance. The median TAT for positive culture was 16 days (IQR 12.5–20.5); for WGS was 35 days (IQR 29.5–38.75) and for subsequent DST was 86 days (IQR 69.5–96.75), resulting in non-WHO regimens for a median of 50.5 days (IQR 28.0–65.0). 9/12 has TB PCRs (Xpert MTB/RIF), with a median TAT of 1 day.ConclusionWGS clearly has a substantial role in our routine UK clinical settings with faster turnaround times in comparison to phenotypic DST. However, the majority of treatment changes defined by WGS were related to isoniazid resistance and given the 1 month TAT for WGS, it would be preferable

Journal article

Berrocal-Almanza LC, Harris RJ, Collin SM, Muzyamba MC, Conroy OD, Mirza A, O'connell A-M, Altass L, Anderson SR, Thomas HL, Campbell C, Zenner D, Phin N, Kon OM, Smith EG, Lalvani Aet al., 2022, Effectiveness of nationwide programmatic testing and treatment for latent tuberculosis infection in migrants in England: a retrospective, population-based cohort study, LANCET PUBLIC HEALTH, Vol: 7, Pages: E305-E315, ISSN: 2468-2667

Journal article

Kon OM, Beare N, Connell D, Damato E, Gorsuch T, Hagan G, Perrin F, Petrushkin H, Potter J, Sethi C, Stanford Met al., 2022, BTS clinical statement for the diagnosis and management of ocular tuberculosis, BMJ OPEN RESPIRATORY RESEARCH, Vol: 9

Journal article

Puranik S, Harlow C, Martin L, Coleman M, Russell G, Park M, Min Kon Oet al., 2022, Monitoring prolongation of QT interval in patients with multidrug-resistant tuberculosis and non-tuberculous mycobacterium using mobile health device AliveCor, Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, Vol: 26, Pages: 1-4, ISSN: 2405-5794

Multidrug resistant tuberculosis and non-tuberculous mycobacterium infections present challenges due to complex treatment regimens. Extended treatment regimes expose patients to higher risks of toxic side-effects. A high drug toxicity profile necessitates closer monitoring. One of the more challenging issues is QTc prolongation with non-injectable regimens.This study investigates the portable AliveCor device to record and measure the QTc on a 6-lead ECG. An automated QTc readout from 12-Lead ECG for each patient (n = 13) and mean QTc value calculated from each patients’ respective AliveCor tracing were compared. The general trend suggests AliveCor underestimates QTc − 92% cases calculated the AliveCor QTc as lower than their corresponding 12-Lead QTc readout.The use of AliveCor could potentially be translated into current clinical practice with caution of percentage variation either side. This could facilitate the use of AliveCor as a promising and convenient screening tool before further evaluation by a 12-Lead ECG is required.

Journal article

Ortiz AT, Coronel J, Vidal JR, Bonilla C, Moore DAJ, Gilman RH, Balloux F, Kon OM, Didelot X, Grandjean Let al., 2021, Genomic signatures of pre-resistance in <i>Mycobacterium tuberculosis</i>, NATURE COMMUNICATIONS, Vol: 12

Journal article

Charania AS, Vergis N, Phillips R, Cornelius V, Katsarou A, Youngstein T, Cook L, Willicombe M, Pilay C, Shturova T, Almonte M, Charania A, Turner R, Kon OM, Cooke G, Thursz M, Cherlin S, Wason J, Milojkovic D, Innes AJ, Cooper Net al., 2021, Multi-Arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate Covid-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial, 63rd ASH Annual Meeting and Exposition, Publisher: American Society of Hematology, Pages: 4200-4200, ISSN: 0006-4971

Conference paper

Kumar K, Kon OM, 2021, Personalised Medicine for Tuberculosis and Non-Tuberculous Mycobacterial Pulmonary Disease, MICROORGANISMS, Vol: 9

Journal article

Dytko O, Park M, Nicholas R, Akshikar R, Kon OMet al., 2021, MOBILE HEALTH USES IN SURVEILLANCE OF TUBERCULOSIS MEDICATION SIDE EFFECTS AND BEYOND-A PILOT STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A81-A81, ISSN: 0040-6376

Conference paper

Evans RA, McAuley H, Harrison EM, Shikotra A, Singapuri A, Sereno M, Elneima O, Docherty AB, Lone NI, Leavy OC, Daines L, Baillie JK, Brown JS, Chalder T, De Soyza A, Diar Bakerly N, Easom N, Geddes JR, Greening NJ, Hart N, Heaney LG, Heller S, Howard L, Hurst JR, Jacob J, Jenkins RG, Jolley C, Kerr S, Kon OM, Lewis K, Lord JM, McCann GP, Neubauer S, Openshaw PJM, Parekh D, Pfeffer P, Rahman NM, Raman B, Richardson M, Rowland M, Semple MG, Shah AM, Singh SJ, Sheikh A, Thomas D, Toshner M, Chalmers JD, Ho L-P, Horsley A, Marks M, Poinasamy K, Wain LV, Brightling CE, PHOSP-COVID Collaborative Groupet al., 2021, Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study, The Lancet Respiratory Medicine, Vol: 9, Pages: 1275-1287, ISSN: 2213-2600

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health bur

Journal article

Manalan K, Testi I, Dixit B, Payadachee Y, Sethi C, Martin L, Russell G, Addison P, Pavesio C, Petrushkin H, Akshikar R, Kon OMet al., 2021, Management of ocular tuberculosis(OTB): The role of CT and Positron Emission Tomography(PET) imaging, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Park M, Coleman M, Martin L, Russell G, Lalvani A, Satta G, Kon OMet al., 2021, Identification of isoniazid mono-resistance is delayed despite whole genome sequencing, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Dhariwal J, Cameron A, Wong E, Trujillo-Torralbo B, Del Rosario A, Bakhsoliani E, Paulsen M, Jackson D, Hansel TT, Edwards M, Cousins D, Walton RP, Johnston SLet al., 2021, Pulmonary innate lymphoid cell responses during rhinovirus-induced asthma exacerbations, Journal of Allergy and Clinical Immunology, Vol: 204, Pages: 1259-1273, ISSN: 0091-6749

Rationale Type 2 innate lymphoid cells (ILC2s) are significant sources of type 2 cytokines, which are implicated in the pathogenesis of asthma and asthma exacerbations. The role of ILC2s in virus-induced asthma exacerbations is not well-characterized. Objectives To characterize pulmonary ILC responses following experimental rhinovirus challenge in patients with moderate asthma and healthy subjects. Methods Patients with moderate asthma and healthy subjects were inoculated with rhinovirus-16, and underwent bronchoscopy at baseline, day 3 and day 8 post-inoculation. Pulmonary ILC1s and ILC2s were quantified in bronchoalveolar lavage (BAL) using flow cytometry. The ratio of BAL ILC2:ILC1 was assessed to determine their relative contributions to the clinical and immune response to rhinovirus challenge. Measurements and Main Results At baseline, ILC2s were significantly higher in patients with asthma than healthy subjects. At day 8, ILC2s significantly increased from baseline in both groups, which was significantly higher in asthma than in healthy subjects (all comparisons P<0.05). In healthy subjects, ILC1s increased from baseline at day 3 (P=0.001), while in patients with asthma, ILC1s increased from baseline at day 8 (P=0.042). Patients with asthma had significantly higher ILC2:ILC1 ratios at baseline (P=0.024) and day 8 (P=0.005). Increased ILC2:ILC1 ratio in asthma correlated with clinical exacerbation severity and type 2 cytokines in nasal mucosal lining fluid. Conclusions An ILC2-predominant inflammatory profile in asthma was associated with increased severity and duration of rhinovirus infection compared with healthy subjects, supporting the potential role of ILC2s in the pathogenesis of virus-induced asthma exacerbations. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01773590

Journal article

Paterson S, Kar S, Ung SK, Gardener Z, Bergstrom E, Ascough S, Kalyan M, Zyla J, Maertzdorf J, Mollenkopf H-J, Weiner J, Jozwik A, Jarvis H, Jha A, Nicholson BP, Veldman T, Woods CW, Mallia P, Kon OM, Kaufmann SHE, Openshaw PJ, Chiu Cet al., 2021, Innate-like gene expression of lung-resident memory CD8+ T-cells during experimental human influenza, American Journal of Respiratory and Critical Care Medicine, Vol: 204, Pages: 826-841, ISSN: 1073-449X

Rationale: Suboptimal vaccine immunogenicity and antigenic mismatch, compounded by poor uptake, means that influenza remains a major global disease. T cells recognizing peptides derived from conserved viral proteins could enhance vaccine-induced cross-strain protection.Objectives: To investigate the kinetics, phenotypes, and function of influenza virus–specific CD8+ resident memory T (Trm) cells in the lower airway and infer the molecular pathways associated with their response to infection in vivo.Methods: Healthy volunteers, aged 18–55, were inoculated intranasally with influenza A/California/4/09(H1N1). Blood, upper airway, and (in a subgroup) lower airway samples were obtained throughout infection. Symptoms were assessed by using self-reported diaries, and the nasal viral load was assessed by using quantitative PCR. T-cell responses were analyzed by using a three-color FluoroSpot assay, flow cytometry with MHC I–peptide tetramers, and RNA sequencing, with candidate markers being confirmed by using the immunohistochemistry results for endobronchial biopsy specimens.Measurements and Main Results: After challenge, 57% of participants became infected. Preexisting influenza-specific CD8+ T cells in blood correlated strongly with a reduced viral load, which peaked at Day 3. Influenza-specific CD8+ T cells in BAL fluid were highly enriched and predominantly expressed the Trm markers CD69 and CD103. Comparison between preinfection CD8+ T cells in BAL fluid and blood by using RNA sequencing revealed 3,928 differentially expressed genes, including all major Trm-cell markers. However, gene set enrichment analysis of BAL-fluid CD8+ T cells showed primarily innate cell–related pathways and, during infection, included upregulation of innate chemokines (Cxcl1, Cxcl10, and Cxcl16) that were also expressed by CD8+ cells in bronchial tissues.Conclusions: CD8+ Trm cells in the human lung display innate-like gene and protein expression that demonstrates blur

Journal article

Padayachee Y, Flicke S, Linton S, Cafferkey J, Min Kon O, Johnston SL, Ellis AK, Desrosiers M, Turner P, Valenta R, Scadding GKet al., 2021, Review: The nose as a route for therapy. Part 2 Immunotherapy, Frontiers in Allergy, Vol: 2, ISSN: 2673-6101

The nose provides a route of access to the body for inhalants and fluids. Unsurprisingly it has a strong immune defense system, with involvement of innate (e.g., epithelial barrier, muco- ciliary clearance, nasal secretions with interferons, lysozyme, nitric oxide) and acquired (e.g., secreted immunoglobulins, lymphocytes) arms. The lattice network of dendritic cells surrounding the nostrils allows rapid uptake and sampling of molecules able to negotiate the epithelial barrier. Despite this many respiratory infections, including SARS-CoV2, are initiated through nasal mucosal contact, and the nasal mucosa is a significant “reservoir” for microbes including Streptococcus pneumoniae, Neisseria meningitidis and SARS -CoV-2. This review includes consideration of the augmentation of immune defense by the nasal application of interferons, then the reduction of unnecessary inflammation and infection by alteration of the nasal microbiome. The nasal mucosa and associated lymphoid tissue (nasopharynx-associated lymphoid tissue, NALT) provides an important site for vaccine delivery, with cold-adapted live influenza strains (LAIV), which replicate intranasally, resulting in an immune response without significant clinical symptoms, being the most successful thus far. Finally, the clever intranasal application of antibodies bispecific for allergens and Intercellular Adhesion Molecule 1 (ICAM-1) as a topical treatment for allergic and RV-induced rhinitis is explained.

Journal article

Kondratiuk AL, Pillay TD, Kon OM, Lalvani Aet al., 2021, A conceptual framework to accelerate the clinical impact of evolving research into long COVID, LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 756-757, ISSN: 1473-3099

Journal article

Morgan C, Barrett J, Brown A, Coughlan C, Subbarao S, Abbara A, John L, Martin L, Lynn W, Russell G, Kon OMet al., 2021, Respiratory samples to diagnose tuberculosis in the absence of chest x-ray abnormalities, RESPIRATORY MEDICINE, Vol: 185, ISSN: 0954-6111

Journal article

Kotecha T, Knight DS, Razvi Y, Kumar K, Vimalesvaran K, Thornton G, Patel R, Chacko L, Brown JT, Coyle C, Leith D, Shetye A, Ben A, Bell R, Captur G, Coleman M, Goldring J, Gopalan D, Heightman M, Hillman T, Howard L, Jacobs M, Jeetley PS, Kanagaratnam P, Kon OM, Lamb LE, Manisty CH, Mathurdas P, Mayet J, Negus R, Patel N, Pierce I, Russell G, Wolff A, Xue H, Kellman P, Moon JC, Treibel TA, Cole GD, Fontana Met al., 2021, Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance, EUROPEAN HEART JOURNAL, Vol: 42, Pages: 1866-1878, ISSN: 0195-668X

Journal article

Vergis N, Phillips R, Cornelius V, Katsarou A, Youngstein T, Cook L, Willicombe M, Pilay C, Shturova T, Almonte M, Charania A, Turner R, Kon OM, Cooke G, Thursz M, Cherlin S, Wason J, Milojkovic D, Innes AJ, Cooper Net al., 2021, Multi-arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate COVID-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial, Trials, Vol: 22, ISSN: 1745-6215

OBJECTIVES: The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: Determine the efficacy of RUX or FOS to reduce mortality Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale* Determine the efficacy of RUX or FOS to reduce systemic inflammation Determine the efficacy of RUX or FOS to the incidence of renal impairment Determine the efficacy of RUX or FOS to reduce duration of hospital stay Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. TRIAL DESIGN: A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care. PARTICIPANTS: Patients will be recruited while inpatients during hospitalisation for COVID-19 in multiple centres throughout the UK including Imperial College Healthcare NHS Trust. INCLUSION: Patients age ≥ 18 years at screening Patients with mild or moderate COVID-19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale Patients meeting criteria: Hospitalization AND SARS-CoV2 infection (clinically suspected or laboratory confirmed) AND Radiological change consistent with COVID-19 disease C

Journal article

Mallia P, Russell G, Meghji J, Wong B, Kumar K, Pilkington V, Chhabra S, Russell B, Chen J, Srikanthan K, Park M, Owles H, Liew F, Alcada J, Martin L, Coleman M, Elkin S, Ross C, Agrawal S, Gardiner T, Bell A, White A, Hampson D, Vithlani G, Manalan K, Bramer S, Martin S, Kucheria A, Ratnakumar P, Sheeka A, Anandan L, Copley S, Bloom C, Kon Oet al., 2021, Symptomatic, biochemical and radiographic recovery in patients with Covid-19, BMJ Open Respiratory Research, Vol: 8, ISSN: 2052-4439

Background: The symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described.Methods: Retrospective analysis of 401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness.Results: 75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge.Conclusions: Patients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19.

Journal article

Halliday A, Jain P, Hoang L, Parker R, Tolosa-Wright M, Masonou T, Green N, Boakye A, Takwoingi Y, Hamilton S, Mandagere V, Fries A, Coin L, Deeks J, White PJ, Levin M, Beverley P, Kon OM, Lalvani Aet al., 2021, New technologies for diagnosing active TB: the VANTDET diagnostic accuracy study, Efficacy and Mechanism Evaluation, Vol: 8, Pages: 1-160, ISSN: 2050-4365

<jats:sec id="abs1-1"> <jats:title>Background</jats:title> <jats:p>Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed.</jats:p> </jats:sec> <jats:sec id="abs1-2"> <jats:title>Objective</jats:title> <jats:p>To validate promising new technologies [namely whole-blood transcriptomics, proteomics, flow cytometry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR)] and existing signatures for the detection of active TB in samples obtained from individuals with suspected active TB.</jats:p> </jats:sec> <jats:sec id="abs1-3"> <jats:title>Design</jats:title> <jats:p>Four substudies, each of which used samples from the biobank collected as part of the interferon gamma release assay (IGRA) in the Diagnostic Evaluation of Active TB study, which was a prospective cohort of patients recruited with suspected TB.</jats:p> </jats:sec> <jats:sec id="abs1-4"> <jats:title>Setting</jats:title> <jats:p>Secondary care.</jats:p> </jats:sec> <jats:sec id="abs1-5"> <jats:title>Participants</jats:title> <jats:p>Adults aged ≥ 16 years presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham, with suspected active TB.</jats:p> </jats:sec> <jats:sec id="abs1-6"> <jats:title>Interventions</jats:title> <jats:p>New tests using genome-wide gene expression microarray

Journal article

Hoang LT, Jain P, Pillay TD, Tolosa-Wright M, Niazi U, Takwoingi Y, Halliday A, Berrocal-Almanza LC, Deeks JJ, Beverley P, Kon OM, Lalvani Aet al., 2021, Transcriptomic signatures for diagnosing tuberculosis in clinical practice: a prospective, multicentre cohort study, LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 366-375, ISSN: 1473-3099

Journal article

Morgan CR, Russell GK, Kon OM, 2021, When to consider tuberculosis: bronchiectasis in the elderly population, BMJ CASE REPORTS, Vol: 14

Journal article

Patterson B, Abbara A, Collin S, Henderson M, Shehata M, Gorgui-Naguib H, Lynn W, Kon OM, John Let al., 2021, Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests, JOURNAL OF INFECTION, Vol: 82, Pages: 240-244, ISSN: 0163-4453

Journal article

Jha A, Thwaites RS, Tunstall T, Kon OM, Shattock RJ, Hansel TT, Openshaw PJMet al., 2021, Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis., Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 694-703.e12, ISSN: 0091-6749

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

Journal article

Agrawal R, Testi I, Bodaghi B, Barisani-Asenbauer T, McCluskey P, Agarwal A, Kempen JH, Gupta A, Smith JR, de Smet MD, Yuen YS, Mahajan S, Kon OM, Quan DN, Pavesio C, Gupta Vet al., 2021, Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2 <i>Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis</i>, OPHTHALMOLOGY, Vol: 128, Pages: 277-287, ISSN: 0161-6420

Journal article

Agrawal R, Testi I, Mahajan S, Yuen YS, Agarwal A, Kon OM, Barisani-Asenbauer T, Kempen JH, Gupta A, Jabs DA, Smith JR, Quan DN, Pavesio C, Gupta Vet al., 2021, Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1 <i>Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis</i>, OPHTHALMOLOGY, Vol: 128, Pages: 266-276, ISSN: 0161-6420

Journal article

Padayachee Y, Cafferkey J, Park M, Kumar K, Martin L, Kon OM, Russel G, Coleman Met al., 2021, NEGATIVE INTERFERON-GAMMA RELEASE ASSAYS RELIABLY RULE OUT PROGRESSION TO ACTIVE TB IN PATIENTS WHO HAVE INFLAMMATORY CONDITIONS AND ARE STARTING BIOLOGIC THERAPY, Publisher: BMJ PUBLISHING GROUP, Pages: A54-A54, ISSN: 0040-6376

Conference paper

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