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COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19.We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733.Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87).Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19.LifeArc and CW+.

Rationale: Chronic obstructive pulmonary disease (COPD) is a condition punctuated by acute exacerbations commonly triggered by viral and/or bacterial infection. Early identification of exacerbation triggers is important to guide appropriate therapy, but currently available tests are slow and imprecise. Volatile organic compounds (VOCs) can be detected in exhaled breath and have the potential to be rapid tissue-specific biomarkers of infection etiology. Objectives: To determine whether volatile organic compound measurement could distinguish viral from bacterial infection in COPD. Methods: We used serial sampling within in vitro and in vivo studies to elucidate the dynamic changes that occur in VOC production during acute respiratory viral infection. Highly sensitive gas chromatography–mass spectrometry techniques were used to measure VOC production from infected airway epithelial-cell cultures and in exhaled breath samples from healthy subjects experimentally challenged with rhinovirus (RV)-A16 and from subjects with COPD with naturally occurring exacerbations. Measurements and Main Results: We identified a novel VOC signature comprising decane and other long-chain alkane compounds that is induced during RV infection of cultured airway epithelial cells and is also increased in the exhaled breath from healthy subjects experimentally challenged with RV and from patients with COPD during naturally occurring viral exacerbations. These compounds correlated with the magnitude of antiviral immune responses, viral burden, and exacerbation severity but were not induced by bacterial infection, suggesting that they represent a specific virus-inducible signature. Conclusions: Our study highlights the potential for measurement of exhaled breath VOCs as rapid, noninvasive biomarkers of viral infection. Further studies are needed to determine whether measurement of these signatures could be used to guide more targeted therapy with antibiotic/antiviral agents for COPD exacerbations.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are episodes of symptom worsening which have significant adverse consequences for patients. Exacerbations are highly heterogeneous events associated with increased airway and systemic inflammation and physiological changes. The frequency of exacerbations is associated with accelerated lung function decline, quality of life impairment and increased mortality. They are triggered predominantly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. A proportion of patients appear to be more susceptible to exacerbations, with poorer quality of life and more aggressive disease progression than those who have infrequent exacerbations. Exacerbations also contribute significantly to healthcare expenditure. Prevention and mitigation of exacerbations are therefore key goals of COPD management.

A number of studies have highlighted physiological data from the first surge in critically unwell Covid-19 patients but there is a paucity of data describing emerging variants of SARS-CoV-2, such as B.1.1.7. We compared ventilatory parameters, biochemical and physiological data and mortality between the first and second COVID-19 surges in the United Kingdom, where distinct variants of SARS-CoV-2 were the dominant stain. We performed a retrospective cohort study investigating critically unwell patients admitted with COVID-19 across three tertiary regional ICUs in London, UK. Of 1782 adult ICU patients screened, 330 intubated and ventilated patients diagnosed with COVID-19 were included. In the second wave where B.1.1.7 variant was the dominant strain, patients were had increased severity of ARDS whilst compliance was greater (p

INTRODUCTION: Public health measures to reduce the transmission of COVID-19 have required various changes in life-style, including loss or risk to employment and social isolation. We wished to assess how these measured effected 30-45 year old smokers at risk of COPD participating in the BLF Early COPD cohort study METHODS: At enrolment, participants were aged 30-45 years, tobacco smokers with >10 pack-year smoking history, FEV1=>80% predicted and a BMI < 35kg/m2. Participants were seen face-to-face in clinic pre-COVID. During lock-down, they were posted questionnaires and contacted by telephone. The last clinic visit took place on the 12 March 2020, remote visits took place between 16 April and 28 Sep. 260 individuals at six sites (25 Belfast, 38 Birmingham, 25 Edinburgh, 101 London, 27 Manchester and 44 Nottingham) were asked about smoking habits. The MRC chronic bronchitis questionnaire, COPD Assessment test (CAT), Leicester cough questionnaire, Hospital Anxiety and Depression questionnaire were completed in writing by the participant and returned by post or photographed and returned by email. At enrolment, the post-BD FEV1 was 3.81 (SD 0.8) litres, 101% (11) of GLI predicted. Comparisons were made by paired t-tests and chi-squared tests. RESULTS: Level of anxiety increased from 6.74 (SD 4.4) to 7.37 (SD 4.7, n=233; p=0.010) during lock-down; depression scores increased from 4.30 (3.9) to 5.14 (SD 4.1; n=233; p

Introduction: The presence of chronic bronchitis (CB) symptoms is associated with increased risk of cardiovascular (CV) disease, especially in those with chronic lung disease. Here, we assessed aortic pulse wave velocity (PWV), a measure of CV risk, in young smokers classified as chronic bronchitic or not. Methods: All participants from the BLF Early COPD Cohort (30-45 years old, current smokers with > 10 pack years smoking and without confirmed COPD at baseline) who underwent aortic PWV (Vicorder, UK) were included. Age, gender, body mass index (BMI), heart rate (HR), blood pressure (BP), post-bronchodilator spirometry (FEV1 %pred) and mean arterial pressure (MAP) were also recorded. Participants were classified as CB or not according to “Do you usually have a productive cough on most days for at least 3 months a year for 2 consecutive years”. Results: Of the 157 subjects, aortic PWV was not different between those classified as chronic bronchitic (n=46) or not (n=111), p=0.634. As expected, male gender, age and MAP were all associated with increased aortic PWV, p Conclusions: Young smokers classified as chronic bronchitic did not have greater aortic stiffness compared to those who were not at the baseline study of the BLF Early COPD cohort.

The rapid global spread and significant mortality associated with the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection has spurred an urgent race to find effective treatments. Repurposing existing drugs is a particularly attractive approach as pharmacokinetic and safety data already exist; thus, development can leapfrog straight to clinical trials of efficacy, generating results far more quickly than de novo drug development. This review summarizes the state of play for the principle drugs identified as candidates to be repurposed for treating COVID-19 grouped by broad mechanism of action: antiviral, immune enhancing, and antiinflammatory or immunomodulatory. Patient selection, particularly with regard to disease stage, is likely to be key. To date, only dexamethasone and remdesivir have been shown to be effective, but several other promising candidates are in trials.

RATIONALE: COPD exacerbations are prone to non-recovery but there are no data about the effectiveness of retreatment on these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event. METHODS: This multi-centre randomised double-blind placebo-controlled trial studied retreatment with oral ciprofloxacin 500mg or matched placebo twice daily for 7 days in patients with GOLD stage II - IV COPD with persistent symptoms and/or serum C-reactive protein (CRP) ≥8mg/L initiated 14 (+/- 3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period. RESULTS: Of 826 patients screened at 4 centres, 144 eligible participants with incomplete recovery were randomised to receive ciprofloxacin (n=72) or placebo (n=72). 57% of patients in the ciprofloxacin group had experienced 1 or more exacerbations, compared to 53% in the placebo group. The median time to the next exacerbation was 32.5 days (IQR 13-50) in the placebo arm and 34 days (IQR 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio = 1.07, 95% CI 0.68-1.68; p=0.76). No significant differences were seen in quality of life scores or lung function between treatment groups. CONCLUSION: In patients with persistent symptoms and/or raised CRP 14 days following a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared to placebo. This suggests that non-recovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with anti-inflammatory therapy.

Rationale: Individuals who will develop chronic obstructive pulmonary disease (COPD) could be identified at an early age before clinical manifestations appear. Objectives: We investigated risk of clinical COPD 10 years later in young adults from the general population with and without early COPD with a focus on smoking exposure. Methods: We included 14,870 individuals aged 20–100 years from the Copenhagen General Population Study with spirometry 10 years apart. Early COPD was defined as baseline FEV(1)/FVC less than the lower limit of normal in individuals aged

Rationale: Raised serum C-Reactive Protein (CRP) 14 days after a COPD exacerbation predicts a second exacerbation, presumably due to persistent inflammation or bacterial infection. We examined if a further exacerbation could be prevented by re-treating incompletely resolved COPD exacerbations using Ciprofloxacin. Methods: This multi-centre randomized double-blind placebo-controlled study assessed retreatment with twice daily oral ciprofloxacin 500mg vs placebo for 7 days in patients whose symptoms and/or CRP had not normalised ( Results: Of 826 COPD patients screened at 4 centres, 144 eligible participants with incomplete recovery at day 12-16 post exacerbation were randomised to ciprofloxacin (n=72) or placebo (n=72). Patients had baseline mean age 69.0, 63.2% male, FEV1 49.5% predicted and CAT score 20.5. Median time to the next exacerbation was 32.5 days (IQR 13-50) in the placebo arm and 34 days (IQR 17-62) in the treatment arm. After pre-specified adjustments for previous exacerbations and site there were no significant differences between the groups (p=0.76) (fig 1). No significant differences were seen in CAT, SGRQ or lung function between treatment groups. Conclusion: In patients with incomplete recovery after a treated COPD exacerbation, an additional course of ciprofloxacin provided no additional benefit relative to placebo.

Objective To evaluate C-reactive protein (CRP), globulin and white blood cell (WBC) count as predictors of treatment outcome in pulmonary tuberculosis (PTB). Methods An observational study of patients with active PTB was conducted at a tertiary centre. All patients had serum CRP, globulin and WBC measured at baseline and at 2 months following commencement of treatment. The outcome of interest was requirement for extension of treatment beyond 6 months. Results There were 226 patients included in the study. Serum globulin 45 g/l was the only baseline biomarker evaluated that independently predicted requirement for treatment extension (OR 3.42, 95%CI 1.597.32, P 0.001). An elevated globulin level that failed to normalise at 2 months was also associated with increased requirement for treatment extension (63.9% vs. 5.1%, P 0.001), and had a low negative likelihood ratio (0.07) for exclusion of requirement for treatment extension. On multivariable analysis, an elevated globulin that failed to normalise at 2 months was independently associated with requirement for treatment extension (OR 6.13, 95%CI 2.2316.80, P 0.001). Conclusions Serum globulin independently predicts requirement for treatment extension in PTB and outperforms CRP and WBC as a predictive biomarker. Normalisation of globulin at 2 months following treatment commencement is associated with low risk of requirement for treatment extension.

Background Clinical, radiological and microbiological criteria inform diagnosis of pulmonary Non-Tuberculous Mycobacteria (NTM) disease and treatment decisions. This multicentre, review aims to characterise NTM disease meeting ATS/IDSA criteria and define factors associated with initiation of treatment. Methods Sputum samples growing NTM from 5 London hospitals between 2010 and 2014 were identified. Data for HIV-negative individuals meeting ATS/IDSA guidelines for pulmonary NTM disease were extracted. Associations between clinical variables and treatment decision were investigated using Chi-squared, Fishers-exact or Mann Whitney tests. Factors associated with treatment in univariate analysis (p < 0.150) were included in a multivariate logistic regression model. Results NTM were identified from 817 individuals' sputum samples. 108 met ATS/IDSA criteria. 42/108 (39%) were initiated on treatment. Median age was 68 (56–78) in the cohort. On multivariate analysis, factors significantly associated with treatment of pulmonary NTM infection were: Cavitation on HRCT (OR: 6.49; 95% CI: 2.36–17.81), presenting with night sweats (OR 4.18; 95% CI: 1.08–16.13), and presenting with weight loss (OR 3.02; 95% CI: 1.15–7.93). Of those treated, 18(43%) have completed treatment, 9(21%) remain on treatment, 10(24%) stopped due to side effects, 5(12%) died during treatment. Mortality was 31% (n = 13) in treated versus 21% (n = 14) in the non-treated cohort. Subgroup analysis of individual NTM species did not observe any differences in treatment initiation or outcomes between groups. Discussion Decision to treat pulmonary NTM infection requires clinical judgement when interpreting clinical guidelines. Factors independently associated with decision to treat in this HIV-negative cohort include cavitation on HRCT and presenting with night sweats or weight loss.

Asthma is a very common respiratory condition with a worldwide prevalence predicted to increase. There are significant differences in airway epithelial responses in asthma that are of particular interest during exacerbations. Preventing exacerbations is a primary aim when treating asthma because they often necessitate unscheduled healthcare visits and hospitalizations and are a significant cause of morbidity and mortality. The most common cause of asthma exacerbations is a respiratory virus infection, of which the most likely type is rhinovirus infection. This article focuses on the role played by the epithelium in orchestrating the innate immune responses to respiratory virus infection. Recent studies show impaired bronchial epithelial cell innate antiviral immune responses, as well as augmentation of a pro-Th2 response characterized by the epithelial-derived cytokines IL-25 and IL-33, crucial in maintaining the Th2 cytokine response to virus infection in asthma. 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 highlight current knowledge regarding the role of viruses and immune modulation in the asthmatic epithelium and to discuss exciting areas for future research and novel treatments.

© 2015 by the American Thoracic Society.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.

Epithelioid hemangioendothelioma (EHE) is a rare malignant cancer of vascular origin that can affect multiple and varied tissue sites. A subtype of EHE, pulmonary epithelioid hemangioendothelioma (PHE), is more unusual with only 200 reported cases. Of these, only 27 have been classified as pleural in origin. Based on available literature, the average age of presentation of pleural PHE is 45.7 years with a male preponderance of 2.375. A summary of all published case reports reveals significant heterogeneity both in presentation and management. Here we add to this knowledge-base with a report of an unusual case of pleural PHE in a 36-year-old female who presented with a 6-week history of chest pain and breathlessness. Significant challenges in the diagnosis and management of patients with pleural PHE exist, including a wide initial differential diagnosis and difficulties in obtaining tissue specimens, coupled with relatively limited treatment options. Early referral to a cardiothoracic center for video-assisted thoracoscopic biopsy is crucial in facilitating a diagnosis and allowing adequate pleural drainage for symptomatic relief. J Clin Med Res. 2015;7(7):566-570 doi: http://dx.doi.org/10.14740/jocmr2174w

Background We describe drug-induced liver injury (DILI) secondary to antituberculous treatment (ATT) in a large tuberculosis (TB) centre in London; we identify the proportion who had risk factors for DILI and the timing and outcome of DILI. Methods We identified consecutive patients who developed DILI whilst on treatment for active TB; patients with active TB without DILI were selected as controls. Comprehensive demographic and clinical data, management and outcome were recorded. Results There were 105 (6.9%) cases of ATT-associated DILI amongst 1529 patients diagnosed with active TB between April 2010 and May 2014. Risk factors for DILI were: low patient weight, HIV-1 co-infection, higher baseline ALP, and alcohol intake. Only 25.7% of patients had British or American Thoracic Society defined criteria for liver test (LT) monitoring. Half (53%) of the cases occurred within 2 weeks of starting ATT and 87.6% occurred within 8 weeks. Five (4.8%) of seven deaths were attributable to DILI. Conclusions Only a quarter of patients who developed DILI had British or American Thoracic Society defined criteria for pre-emptive LT monitoring, suggesting that all patients on ATT should be considered for universal liver monitoring particularly during the first 8 weeks of treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2330-z) contains supplementary material, which is available to authorized users.

Lydia J Finney,1 Andrew Ritchie,1 Elizabeth Pollard,2 Sebastian L Johnston,1 Patrick Mallia1 1Airway Disease Infection Section, National Heart and Lung Institute, Imperial College, London, United Kingdom; 2King's College London, London, United Kingdom Abstract: Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans. Keywords: chronic obstructive pulmonary disease, Haemophilus influenzae, nontypeable Haemophilus influenzae, respiratory viruses, vaccination

Purpose of review The emergence of next-generation 16S rRNA sequencing techniques has facilitated a more detailed study of the body's microbiota and led to renewed interest in the association between microbial exposure and asthma inception. In this review, we evaluate the evidence that the respiratory tract and intestinal microbiota contribute to asthma pathogenesis and progression. Recent findings Human studies have revealed associations between the presence of potentially pathogenic bacteria in the respiratory tract in early life and subsequent risk of allergic sensitization and asthma. Similarly, alterations in the intestinal microbiota of neonates have also been shown to precede the development of asthma. Emerging evidence suggests that the lung microbiota is dysregulated in asthma with specific changes in bacterial diversity and community composition according to severity and phenotype. Studies using germ-free mice have been invaluable in moving our understanding from correlation to causation by demonstrating a mechanistic link between the neonatal microbiota and the development of allergic airway inflammation. Summary An expanding body of literature supports the hypothesis that early life microbial exposures and bacterial communities within the lung and/or intestine play an important role in shaping early immunological development. Perturbations in the microbiota may promote immune defects associated with the development of asthma and allergic sensitization.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of global morbidity and mortality worldwide. The clinical course of both asthma and COPD are punctuated by the occurrence of exacerbations, acute events characterized by increased symptoms and airflow obstruction. Exacerbations contribute most of the morbidity, mortality and excess healthcare costs associated with both asthma and COPD. COPD and asthma exacerbations are frequently associated with respiratory virus infections and this has led to an intense research focus into the mechanisms of virus-induced exacerbations over the past decade. Current therapies are effective in reducing chronic symptoms but are less effective in preventing exacerbations, particularly in COPD. Understanding the mechanisms of virus-induced exacerbation will lead to the development of new targeted therapies that can reduce the burden of virus-induced exacerbations. In this review we discuss current knowledge of virus-induced exacerbations of asthma and COPD with a particular focus on mechanisms, human studies, virus–bacteria interactions and therapeutic advances.

Background The aim of this study was to evaluate C-reactive protein(CRP), globulin and white cell count as predictors of treatment outcome in pulmonary tuberculosis. Methods An observational study of patients with active pulmonary tuberculosis was conducted at a tertiary centre. All patients had serum CRP, globulin and white cell count measured at baseline and two months following commencement of therapy. The outcome of interest was requirement for extension of therapy beyond 6 months. Results There were 226 patients included in the study. Serum globulin >45 g/L was the only baseline biomarker evaluated that independently predicted requirement for therapy extension (OR 3.59 (1.79–7.57; p Conclusions Serum globulin independently predicts requirement for treatment extension in pulmonary TB and outperforms CRP and white cell count as a predictive biomarker. Normalisation of globulin at two months following treatment commencement is associated with low risk of requirement for treatment extension.

Introduction Non-Tuberculous Mycobacteria (NTM) are ubiquitous in the environment meaning clinical, radiological and microbiological criteria are important in diagnosing NTM lung disease. A multicentre, retrospective review was performed to characterise NTM disease within our region and describe the outcomes of current management. Methods All NTM positive sputum samples received by the National Mycobacterium Reference Laboratory (NMRL) from Imperial College NHS Healthcare and North West London Hospitals NHS Trusts between 2010–2014 were extracted. HIV-negative individuals with ≥2 positive sputum samples or ≥1 positive bronchoalveolar lavage were included. Demographic, clinical, radiological, microbiological, management and outcome data was obtained from electronic records. Results 1190 NTM sputum samples were identified from 822 individuals. 152 individual patients met inclusion criteria for analysis. Table 1 describes cohort demographics. Within the cohort 48/152 (32%) were treated for NTM disease. All treated subjects and 74/104 (71%) non-treated subjects met international guidelines for diagnosis of NTM infection, which included positive clinical, radiological (cavities or bronchiectasis +/- nodules or infiltrates) and microbiological criteria. Mycobacterium avium complex (MAC) was the most commonly isolated (68/152; 45%) and treated organism (21/48; 44%) followed by Mycobacterium kansasii (11/48; 23%). 19/48 (40%) completed treatment (median duration: 17 months [IQR: 12–24]). 10/48 (21%) remain on treatment (median duration: 18 months [IQR: 11–36]), 11/48 (23%) stopped treatment due to side effects and 13/48 (27%) were either lost to follow up or treated for Mycobacterium tuberculosis . Of those treated, 29/48 (60%) culture converted; 23/29 (79%) remain negative at 12 months post culture conversion. Of 19/48 who completed treatment, 5/19 (26%) had symptomatic or radiological disease progression compared to 11/28 (39%) who did not complete treatment. 11/48 (23%) patients died within the treatment group. Within the untreated subjects who met international guidelines for NTM infection (74/104), mortality was 19/74 (26%) (p = 0.83). Discussion NTM is a challenging disease with only 39% of eligible subjects receiving treatment and a high associated mortality. Furthermore, only 40% starting treatment completed it and the 21% who remain on treatment have been treated for a median duration of 18 months to date. Unlike similar HIV-negative UK cohorts, MAC pulmonary disease is the most prevalent.

Introduction We describe the incidence and management of drug induced liver injury (DILI) in active TB at the largest UK centre, using a nurse-led local protocol derived from 1998 BTS guidelines. Methods All active TB cases were identified from April 2010 to May 2014. Patients were identified with DILI by following criteria: Type 1 DILI(ALT >3x upper limit normal (ULN-55iu/l), Type 2 DILI (ALP >2x ULN(150 iu/l) and Bilirubin >21 iu/l) or Type 3 DILI (Bilirubin >40 iu/l). Patient demographics, TB treatment (ATT), timing, management and outcomes of DILI were described. Baseline characteristics and ATT doses were matched with controls. Results 105 individuals with DILI were identified out of 1529 patients with active TB (6.9%). 81% were on standard first line therapy (Rifampicin (R), Isoniazid (H), Pyrazinamide (Z) and Ethambutol (E)). 7.8% were on Moxifloxacin (M) instead of E and 1.9% were on RHME. Type 1 DILI was most frequent (81%) with median peak ALT 296 iu/l (IQR 227–505). Median time from treatment start to onset of DILI was 12.5 days (7–30). Symptoms at presentation included nausea/vomiting (54%), abdominal pain (18%) and jaundice (12.4%). 45.7% patients had all medication stopped, 7.6% continued ethambutol with amikacin (A), 26.7% continued all medication, 6.7% stopped Z only, 3.8% substituted Z for a quinolone. Median time from stopping to reintroduction was 10 days (6–17). Of 66 reintroduction patients, regimens included H >R >E(45%), H>R>E>M (31%) and R>E>M (15%). Median time from reintroduction to full treatment restart was 14 days (12–18). 81% of patients were uneventfully reintroduced, 5% suffered a 2nd DILI. 32% patients required hospital admission and 4(3.8%) died. DILI cases were matched to 200 controls. Cases more likely (P Conclusion DILI remains the most important toxicity of ATT and usually occurs during the first month. The BTS guideline provides a useful template for the diagnosis and management of DILI which may be largely nurse led and ambulatory. Most patients are successfully reintroduced without pyrazinamide. HIV status, body weight and quinolone use are risk factors.