Graham Bothamley

Homerton University Hospital NHS Foundation Trust · Department of Respiratory Medicine

Objective: To determine the current use and potential acceptance (by tuberculosis experts worldwide) of novel rapid tests for the diagnosis of tuberculosis that are in line with World Health Organization target product profiles. Methods: A multilingual survey was disseminated online between July and November of 2016. Results: A total of 723 individ...

Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (...

Introduction 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H) resistant (Hr) tuberculosis recommend a four-drug regimen- rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx)- with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx)...

European-Respiratory-Society (ERS) International Congress, Madrid, SPAIN, SEP 28-OCT 02, 2019

2018 World Health Organization (WHO) guidelines for isoniazid resistant (INH-R) tuberculosis recommend a treatment regimen of four drugs continuously for six months- rifampicin, pyrazinamide, ethambutol, and levofloxacin; with or without isoniazid ([H]RZE-Lfx)- once drug sensitivity testing results are known.¹ In the context of a high-income settin...

Background Despite a recent decline in the annual incidence of tuberculosis (TB) in the UK, rates remain higher than in most Western European countries. The detection and treatment of latent TB infection (LTBI) is an essential component of the UK TB control programme. Objectives To assess the prognostic value and cost-effectiveness of the current...

Setting: Although cough in tuberculosis (TB) is presumed to be important for transmission, there is little objective supporting evidence. Objective: To describe 24-h cough frequency in a group with TB, and investigate associations with household rates of infection. Design: Patients with a new diagnosis of pulmonary TB underwent 24-h cough freq...

Background: Tackling tuberculosis requires testing and treatment of latent tuberculosis in high-risk groups. The aim of this study was to estimate the predictive values of the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs) for the development of active tuberculosis in high-risk groups-ie, people in recent contact with activ...

We conducted a cross-sectional analysis of baseline data from a UK cohort study which enrolled participants at risk of latent tuberculosis infection (LTBI, defined as a positive result for either of the two interferon gamma release assays). Binomial regression with a log link was used to estimate crude and adjusted prevalence ratios (PRs) and 95% C...

Rationale and Objectives Chest X-rays (CXR) are one of the most frequently requested imaging examinations and are fundamental to many patient pathways. The aim of this study was to investigate the diagnostic accuracy of CXR interpretation by reporting radiographers (technologists). Methods A cohort of consultant radiologists (n = 10) and reporting...

Background: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less and cure rates are even lower. Methods: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatme...

Introduction To compare the clinical chest radiograph (CXR) reports provided by consultant radiologists and reporting radiographers with expert thoracic radiologists. Methods Adult CXRs (n = 193) from a single site were included; 83% randomly selected from CXRs performed over one year, and 17% selected from the discrepancy meeting. Chest radiograp...

Background Tackling tuberculosis (TB) requires testing and treatment of high-risk groups for latent tuberculosis infection. We estimated the predictive values of the tuberculin skin test (TST) and interferon gamma release assays (IGRAs) for development of active TB in migrants and contacts of active TB patients in the UK. Methods Participants were...

Aim: Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. Methods: TBNET is a pan-European clinical research collaboration for tube...

Introduction and objectives The afferent receptor TRPV1 is implicated in the cough reflex. Several single nucleotide polymorphisms (SNPs) in TRPV1 appear to be associated with symptoms of cough in the general population.¹ We investigated whether such SNPs are associated with the objective measures of cough reflex sensitivity and 24-hour cough frequ...

Background Objectives: To determine whether the incidence of tuberculosis with pregnancy is more common than would be expected from the crude birth rate; to see whether there is significant delay in the diagnosis of tuberculosis during pregnancy. Method Design: A cross-sectional survey. Setting: 13 tuberculosis clinics within different European cou...

Background Inflammatory response following initial improvement with anti-tuberculosis (TB) treatment has been termed a paradoxical reaction (PR). HIV co-infection is a recognised risk, yet little is known about other predictors of PR, although some biochemical markers have appeared predictive. We report our findings in an ethnically diverse populat...

No evidence exists on tuberculosis (TB) and latent TB infection (LTBI) management policies among refugees in European countries. A questionnaire investigating screening and management practices among refugees was sent to 38 national TB programme representatives of low and intermediate TB incidence European countries/territories of the WHO European...

The breadth and quality of scientific presentations on clinical and translational research into respiratory infections at the 2015 European Respiratory Society (ERS) International Congress in Amsterdam, the Netherlands, establishes this area as one of the leadings fields in pulmonology. The host–pathogen relationship in chronic obstructive pulmonar...

Tuberculosis (TB) is a major cause of mortality from an infectious disease, globally affecting 9.6 million cases, with 1.5 million deaths in 2014 [1]. In 2014, there were 273 381 TB cases reported in the World Health Organization (WHO) European region, and an estimated 33 000 deaths [2]. Vulnerable populations ( i.e . individuals affected by discri...

Chronic cough is common in the community and can cause significant morbidity. It is not clear how closely treatment guidelines are used in general practice, or how often specialist referral is indicated. We aimed to assess the management of chronic cough in primary care before referral to a cough clinic, and to assess the outcome of managing chroni...

Introduction and objective Cough is prominent in pulmonary tuberculosis (TB) and transmits infection, yet no tool has been validated for assessing cough symptoms. We evaluated the Leicester Cough Questionnaire (LCQ) for measuring cough-related quality of life (QOL) in TB. Method The face validity of the LCQ was evaluated by structured interviews wi...

Introduction and objective Cough is predominant in pulmonary tuberculosis and transmits infection, yet it is unclear how rapidly it responds to treatment. We explored changes in objectively-measured cough frequency during TB therapy with respect to other markers of disease. Method Before or on commencing anti-tuberculous treatment, consecutive pati...

Background: Coughing is important in the transmission of tuberculosis (TB). It is not known if characteristics of cough in TB are distinct and whether they are clinically useful. Aims: To compare temporal patterns of coughing in TB to those in COPD and refractory chronic cough. Methods: Patients with stable COPD, refractory chronic cough and newly-...

Extract The recent European Respiratory Society (ERS) Task Force Report on chronic cough [1] should be commended for drawing attention to a neglected area of respiratory medicine and discussing controversies surrounding the approach to this common clinical problem. Cough hypersensitivity syndrome is proposed as a new shorthand to refer to patient-r...

Latent infection with Mycobacterium tuberculosis is defined by a positive interferon-γ release assay (IGRA) result in the absence of active tuberculosis. Only few, mostly monocentric studies have evaluated the role of IGRAs to predict the development of tuberculosis in recent contacts in low incidence countries of tuberculosis. We analyzed IGRA res...

Drug-resistant Mycobacterium tuberculosis is challenging elimination of tuberculosis (TB). We evaluated risk factors for TB and levels of second-line drug resistance in M. tuberculosis in patients in Europe with multidrug-resistant (MDR) TB. A total of 380 patients with MDR TB and 376 patients with non-MDR TB were enrolled at 23 centers in 16 count...

Technical Appendix. Additional information for TBNET study of multidrug-resistant tuberculosis in Europe, 2010–2011.

Introduction. Patterns of cough in tuberculosis influence transmission of disease yet have been little studied. We report the prevalence, duration, severity and frequency of coughing in tuberculosis. Method. The first part was a retrospective review of the medical records of all individuals diagnosed with pulmonary tuberculosis (PTB) at our hospita...

Background Interferon-gamma release assays (IGRAs) are being used to confirm significant exposure to tuberculosis (TB) after a positive tuberculin skin test (TST). We explored the variability of a positive test in a large UK TB clinic amongst contacts of active disease. Methods The records of all individuals notified with active TB and of their scr...

Cough is a predominant feature of respiratory infection and, in tuberculosis, is of prime importance for transmitting infection. Tuberculosis is transmitted by the air, yet the process by which bacilli are aerosolized has received little attention. Features of cough may account for differences in transmission rates from source cases of pulmonary di...

To the Editor: Tuberculosis is one of the leading causes of morbidity and mortality worldwide [1]. Rapid identification of contagious tuberculosis patients and effective treatment are necessary to prevent the spread of Mycobacterium tuberculosis , the causative bacterium of the disease. Although interferon-γ release assays (IGRAs) have been devel...

Background Cough causes morbidity and transmits disease yet has been under-researched. The best method for recognising and counting coughs remains unclear. We tested the accuracy of the human ear and measured the influence of visual data on cough counting. We also evaluated PulmoTrack®, a potentially fully-automated cough monitor. Methods Consiste...

Michelsen and colleagues1 usefully add to the evidence for the protective effect of BCG against active TB. However, we are puzzled by the conclusion that BCG also prevents Mycobacterium tuberculosis (Mtb) infection. Others have similarly used interferon gamma release assay (IGRA) responses as a surrogate for Mtb infection with similar conclusions.2...

BCG protects against primary tuberculosis, but evidence for protection against infection with Mycobacterium tuberculosis remains controversial. Roy and colleagues merely showed that previous BCG vaccination is associated with a reduced frequency of positive interferon γ release assay (IGRA) results in children recently exposed to M tuberculosis .1...

Introduction. Coughing hinders EBUS and aerosolises secretions. Predictors of cough in bronchoscopy and methods of quantifying it are poorly described. Method. Successive patients wore an audio recorder and microphone immediately before, during and after EBUS. Each recording was analysed by one of three authors; half were re-analysed by the main a...

Aim To examine the adult chest radiograph (CXR) reporting performance of a reporting radiographer in clinical practice using different audit systems; single radiologist and two radiologists, with clinical review of discordant cases. Materials and methods 100 chest radiographs (CXRs) were drawn randomly from a consecutive series of 4800 CXRs which...

Monoclonal antibodies restricted to Mycobacterium tuberculosis can measure epitope-specific antibody levels in a competition assay. Immunodominant epitopes were defined from clinical samples and related to the clinical spectrum of disease. Antibody to the immunodominant epitopes was associated with HLA-DR15. Occupational exposure showed a different...

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, soc...

Unlabelled: The Mycobacterium tuberculosis genome includes the large family of pe_pgrs genes, whose functions are unknown. Because of precedents in other pathogens in which gene families showing high sequence variation are involved in antigenic variation, a similar role has been proposed for the pe_pgrs genes. However, the impact of immune selecti...

TB is still a global problem, with a prevalence of 12 million in 2010. The WHO recommends screening for TB in pregnancy. In areas of high TB incidence, isoniazid should be given as preventive therapy in pregnant women with HIV infection who do not have active TB. This review examines the evidence for this recommendation, reviews advances in diagnos...

Introduction Cough is the unique respiratory symptom. Although associated with a range of conditions it has been little studied in acute respiratory disease. We describe cough frequency and cough-related quality of life in this group. Method Participants had a diagnosis of acute exacerbation of asthma (asthma), chronic obstructive pulmonary disease...

Background Obstructive Sleep Apnoea (OSA) is prevalent in obese patients and has substantial impact on health and society1. We undertook this analysis to examine changes in Sleep Apnoea severity by studying the Apnoea-Hypopnoea Index (AHI) pre and post bariatric surgery in a London District General Hospital. Methods We retrospectively reviewed pati...

Tuberculosis caused 20% of all human deaths in the Western world between the seventeenth and nineteenth centuries and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlie...

Study profile. (PPT)

Ethnic variation in inflammatory profile after completion of intensive-phase antituberculous therapy: participants allocated to placebo only. Patients of African ancestry had lower neutrophil counts (A), lower serum concentrations of CCL2, CCL11, CXCL8 and DBP (B–E) and lower levels of antigen-simulated CCL11 (F), but higher serum concentrations of...

Immunological parameters investigated. (DOCX)

Differences in inflammatory profile in PTB patients of African vs. Eurasian ancestry after completion of intensive-phase antimicrobial therapy: participants allocated to placebo arm only. (DOCX)