Search

Background Changes in brain structure and cognitive decline occur in Chronic Obstructive Pulmonary Disease (COPD). They also occur with smoking and coronary artery disease (CAD), but it is unclear whether a common mechanism is responsible. Methods Brain MRI markers of brain structure were tested for association with disease markers in other organs. Where possible, principal component analysis (PCA) was used to group markers within organ systems into composite markers. Univariate relationships between brain structure and the disease markers were explored using hierarchical regression and then entered into multivariable regression models. Results 100 participants were studied (53 COPD, 47 CAD). PCA identified two brain components: brain tissue volumes and white matter microstructure, and six components from other organ systems: respiratory function, plasma lipids, blood pressure, glucose dysregulation, retinal vessel calibre and retinal vessel tortuosity. Several markers could not be grouped into components and were analysed as single variables, these included brain white matter hyperintense lesion (WMH) volume. Multivariable regression models showed that less well organised white matter microstructure was associated with lower respiratory function (p = 0.028); WMH volume was associated with higher blood pressure (p = 0.036) and higher C-Reactive Protein (p = 0.011) and lower brain tissue volume was associated with lower cerebral blood flow (pp = 0.001). Smoking history was not an independent correlate of any brain marker. Conclusions Measures of brain structure were associated with a range of markers of disease, some of which appeared to be common to both COPD and CAD. No single common pathway was identified, but the findings suggest that brain changes associated with smoking-related diseases may be due to vascular, respiratory, and inflammatory changes.

Background Brain damage and cardiovascular disease are extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD). Cardiovascular risk factors and smoking are contributors to neurodegeneration. This study investigates whether there is a specific, COPD-related deterioration in brain structure and function independent of cardiovascular risk factors and smoking. Materials and methods Neuroimaging and clinical markers of brain structure (micro- and macro-) and function (cognitive function and mood) were compared between 27 stable COPD patients (age: 63.0±9.1 years, 59.3% male, forced expiratory volume in 1 second [FEV1]: 58.1±18.0% pred.) and 23 non-COPD controls with >10 pack years smoking (age: 66.6±7.5 years, 52.2% male, FEV1: 100.6±19.1% pred.). Clinical relationships and group interactions with brain structure were also tested. All statistical analyses included correction for cardiovascular risk factors, smoking, and aortic stiffness. Results COPD patients had significantly worse cognitive function (p=0.011), lower mood (p=0.046), and greater gray matter atrophy (p=0.020). In COPD patients, lower mood was associated with markers of white matter (WM) microstructural damage (p

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.

BackgroundChronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population.ObjectivesWe hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD.MethodsNovel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software.ResultsRetinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02).ConclusionsNon-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk.

IntroductionCigarette smoking and oxidative stress are common risk factors for the multi-morbidities associated with chronic obstructive pulmonary disease (COPD). Elevated levels of advanced glycation endproducts (AGE) increase the risk of cardiovascular disease (CVD) comorbidity and mortality. The enzyme fructosamine-3-kinase (FN3K) reduces this risk by lowering AGE levels.MethodsThe distribution and expression of FN3K protein in lung tissues from stable COPD and control subjects, as well as an animal model of COPD, was assessed by immunohistochemistry. Serum FN3K protein and AGE levels were assessed by ELISA in patients with COPD exacerbations receiving metformin. Genetic variants within the FN3K and FN3K-RP genes were evaluated for associations with cardiorespiratory function in the Subpopulations and Intermediate Outcome Measures in COPD Study cohort.ResultsThis pilot study demonstrates that FN3K expression in the blood and human lung epithelium is distributed at either high or low levels irrespective of disease status. The percentage of lung epithelial cells expressing FN3K was higher in control smokers with normal lung function, but this induction was not observed in COPD patients nor in a smoking model of COPD. The top five nominal FN3K polymorphisms with possible association to decreased cardiorespiratory function (pDiscussionThe data highlight that low and high FN3K expressors exist within our study cohort and metformin induces FN3K levels, highlighting a potential mechanism to reduce the risk of CVD comorbidity and mortality.

BACKGROUND: Chronic obstructive pulmonary disease (COPD; including chronic bronchitis and emphysema) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. Long‐term antibiotic use may reduce both bacterial load and inflammation in the airways. Studies have shown a reduction of exacerbations with antibiotics in comparison to placebo in people with COPD, but there are concerns about antibiotic resistance and safety. OBJECTIVES: To compare the safety and efficacy of different classes of antibiotics (continuous, intermittent or pulsed) for prophylaxis of exacerbations in patients with COPD. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was conducted on 6 February 2019. SELECTION CRITERIA: Randomised controlled trials (RCTs) were selected that compared one prophylactic antibiotic with another in patients with COPD. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data and assessed risk of bias. Discrepancies were resolved by involving a third review author. MAIN RESULTS: We included two RCTs, both published in 2015 involving a total of 391 participants with treatment duration of 12 to 13 weeks. One RCT compared a quinolone (moxifloxacin pulsed, for 5 days every 4 weeks), with a tetracycline (doxycycline continuous) or a macrolide (azithromycin intermittent). The second RCT compared a tetracycline (doxycycline continuous) plus a macrolide (roxithromycin continuous), with roxithromycin (continuous) alone. The trials recruited participants with a mean age of 68 years, with moderate‐severity COPD. Both trials included participants who had between two and five exacerbations in the previous one to two years. In one trial, 17% of patients had previously been using inhaled corticosteroids. In the other study, all patients were positive for Chlamydophila pneumoniae (C pneumoniae). Overall, we judged the evidence presented to be of very low‐certainty, mainly due to imprecision, but we also had concerns about indirectness and methodological quality of the included studies. The primary outcome measures for this review included exacerbations, quality of life, drug resistance and serious adverse events. Macrolide + tetracycline versus macrolide There was no clear difference between treatments in improvement in quality of life as assessed by the Chronic Respiratory Questionnaire (CRQ). The CRQ scale ranges from 0 to 10 and higher scores on the scale indicate better quality of life. CRQ sub‐scales for dyspnoea (mean difference (MD) 0.58, 95% confidence interval (CI) ‐0.84 to 2.00; 187 participants; very low‐certainty evidence), fatigue (MD 0.02, 95% CI ‐1.08 to 1.12; 187 participants; very low‐certainty evidence), emotional function (MD ‐0.37, 95% CI ‐1.74 to 1.00; 187 participants; very low‐certainty evidence), or mastery (MD ‐0.79, 95% CI ‐1.86 to 0.28; 187 participants; very low‐certainty evidence) at 12 weeks. For serious adverse events, it was uncertain if there was a difference between combined roxithromycin and doxycycline versus roxithromycin alone at 48 weeks follow‐up after active treatment of 12 weeks (odds ratio (OR) 1.00, 95% CI 0.52 to 1.93; 198 participants; very low‐certainty evidence). There were five deaths reported in the combined treatment arm, versus three in the single treatment arm at 48 weeks follow‐up after active treatment of 12 weeks (OR 1.63, 95% CI 0.38 to 7.02; 198 participants; very low‐certainty evidence). Quinolone versus tetracycline There was no clear difference between moxifloxacin and doxycycline for the number of participants experiencing one or more exacerbations (OR 0.44, 95% CI 0.14 to 1.38; 50 participants, very low‐certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes. Quinolone versus macrolide There was no clear difference between moxifloxacin and azithromycin for the number of participants experiencing one or more exacerbations (OR 1.00, 95% CI 0.32 to 3.10; 50 participants; very low‐certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes. Marcolide versus tetracycline There was no clear difference between azithromycin and doxycycline for the number of participants experiencing one or more exacerbations (OR 0.44, 95% CI 0.14 to 1.38; 50 participants; very low‐certainty evidence) at 13 weeks. There were no serious adverse events or deaths reported in either treatment groups. We did not identify any evidence for our other primary outcomes. We did not find head‐to‐head evidence for impact of antibiotics on drug resistance. AUTHORS' CONCLUSIONS: It is not clear from the evidence included in this review whether there is a difference in efficacy or safety between different classes or regimens of prophylactic antibiotic, given for 12 to 13 weeks to people with COPD. Whilst no head‐to‐head comparisons of antibiotic resistance were identified, concerns about this continue. The sample size in this review is small and both included studies are of short duration. Thus, there is considerable uncertainty in effects observed and the effects of different prophylactic antibiotics requires further research.

OBJECTIVE: To assess the impact of home telemonitoring on health service use and quality of life in patients with severe chronic lung disease. DESIGN: Randomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring. PARTICIPANTS: 68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of

Background Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome. Methods This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool. Results 52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. Conclusion Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. Trial registration number ISRCTN66148745 and NCT01247870.

Mohani-Preet K Bajaj,1 Daniel R Burrage,2 Andrew Tappouni,3 James W Dodd,4 Paul W Jones,2 Emma H Baker2 1Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, London, UK; 2Clinical Pharmacology, Institute of Infection and Immunity, St George’s University of London, London, UK; 3St George’s University of London, London, UK; 4Academic Respiratory Unit, University of Bristol, Bristol, UK Purpose: People with COPD have cognitive dysfunction, which is greater in those hospitalized for exacerbations than in stable outpatients. We tested the hypothesis that cognitive dysfunction at exacerbation is a disease-specific feature of COPD, rather than a nonspecific feature of hospitalization for acute illness, by comparing cognition between patients hospitalized for acute COPD exacerbations and those with worsening heart failure (HF). Patients and methods: A total of 40 hospital inpatients were recruited, 20 patients with COPD exacerbations and 20 patients with congestive or left-sided HF. Exclusion criteria included previous stroke, known neurological disease, and marked alcohol excess. Participants completed the Montreal cognitive assessment (MoCA) and Hospital Anxiety and Depression Scale (HADS) and underwent spirometry and review of clinical records. Results: Age (mean±SD, COPD 73±10; HF 76±11years), acute illness severity (Acute Physiology and Chronic Health Evaluation [APACHE]-II, COPD 15.4±3.5; HF 15.9±3.0), comorbidities (Charlson index, COPD 1.3±1.9; HF 1.6±1.5), and educational background were similar between COPD and HF groups. MoCA total was significantly lower in COPD than in HF (COPD 20.6±5.6; HF 24.8±3.5, P=0.007); however, significance was lost after correction for age, sex, and pack year smoking history. When compared with HF patients, the COPD cohort performed worse on the following domains of the MoCA: visuospatial function (median [IQR], COPD 0 [1]; HF 2 [1], P=0.003), executive function (COPD 2 [1]; HF 3 [1], P=0.035), and attention (COPD 4 [3]; HF 6 [2], P=0.020). Age (P=0.012) and random glucose concentration (P=0.041) were associated with cognitive function in whole group analysis, with pack year smoking history reaching borderline significance (P=0.050). Conclusion: Total MoCA score for COPD and HF indicated that both groups had mild cognitive impairment, although this was greater in people with COPD. Mechanisms underlying the observed cognitive dysfunction in COPD remain unclear but appear related to blood glucose concentrations and greater lifetime smoking load. Keywords: Montreal cognitive assessment, cognition, comorbidities, systemic, smoking, hyperglycemia

Introduction and objectives COPD patients are more likely to die from cardiovascular disease than from their lung disease. However, under diagnosis of vascular risk factors is common. The aim of this study was to evaluate prevalence and control of cardiovascular risk factors in COPD patients. Methods This was a cross-sectional study of stable COPD outpatients (no exacerbation for >6 weeks). Prior diagnosis and treatment of hypertension, dyslipidaemia and diabetes was recorded. Participants underwent spirometry and measurement of blood pressure, fasting blood lipid profile, plasma glucose and glycated haemoglobin (HbA1c). Hypertension was defined as a blood pressure ≥140/90 mmHg; type 2 diabetes was defined as HbA1c≥48 mmol/mol or fasting plasma glucose ≥7.0 mmol/L, and need for lipid-lowering therapy was based on QRISK2 score ≥10%. Blood pressure was considered controlled if Results 56 participants were recruited (age 69±8 years, 36 (64%) male, 47±25 pack years, FEV1% predicted 55±24 [means ±SD]). 45 (80%) participants had hypertension, 53 (95%) participants had a diagnosis of hyperlipidaemia or met the threshold for lipid-lowering therapy, and 6 (11%) participants had type 2 diabetes. The table 1 shows the proportion of participants with hypertension, hyperlipidaemia and type 2 diabetes who had an existing diagnosis (controlled), an existing diagnosis (uncontrolled) or a new diagnosis. Conclusions In this study around a third of patients had undiagnosed hypertension, and a third met the threshold for requiring lipid lowering therapy. Even in patients who had existing diagnoses, the majority were uncontrolled. In view of the high burden of cardiovascular disease in COPD patients, more attention needs to be given to assessment, treatment and monitoring of cardiovascular risk.

Background: COPD, cardiovascular disease and structural brain disease commonly coexist, but the relative contributions of COPD and cardiovascular disease to structural brain disease is unclear. Aim: The aim of this study was to determine the association between two different COPD phenotypes and structural brain disease. Methods: COPD patients were recruited from two populations. Group 1 were recruited from people attending for elective coronary angiography who had no exacerbations in the preceding year. Group 2 were recruited from people attending the respiratory outpatient department who had had at least 1 exacerbation in the preceding year. Participants underwent measurement of Framingham score (10-year risk of cardiovascular event), spirometry, arterial stiffness, skin capillary density, cardiac biomarkers, systemic inflammatory markers and structural brain MRI. Results: Group 1 had mild/moderate COPD with significantly higher cardiovascular risk whereas group 2 had moderate/severe COPD with lower cardiovascular risk (FEV1 % predicted 78±19 v 54±24 p Conclusion: Cardiovascular risk, rather than respiratory health, appears more strongly associated with white matter brain disease in these two groups of patients with COPD.

Background: People with COPD have reduced physical activity and increased cardiometabolic disease. Understanding the relationship between different types of inactivity and cardiometabolic impairment is important to design appropriate interventions Aim: To determine the effects of physical inactivity and sedentary behaviour on cardiometabolic profiles in COPD patients Methods: Stable COPD patients underwent actigraphy over 8 days. Physical inactivity was defined as Results: Metabolic syndrome was more common in high (SE 71%, CP 66%) than low sedentary groups (BB 20%, LM 0%, p=0.01). High sedentary patients had greater insulin resistance (HOMA2IR) (SE 2.2±1.0, CP 3.1±2.2, BB 1.5±0.7, LM 0.9±0.4, p=0.028) and lower HDL cholesterol (SE 1.7±0.5, CP 1.5±0.5, BB 2.2±1.0, LM 2.4±0.6, p=0.015). On univariate analysis, after adjustment for age and gender, sedentary behaviour determined HOMA2IR and HDL, independent of physical activity Conclusions: Sedentary behaviour was associated with worse cardiometabolic profile, independent of physical activity. Interventions to promote non-sedentary behaviour could improve cardiometabolic profiles, even in COPD patients unable to achieve moderate intensity activity

Background Loss of muscle mass is a co-morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor-15 (GDF-15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF-15 may contribute to muscle wasting in COPD. Methods We determined the expression of GDF-15 in the serum and muscle of patients with COPD and analysed the association of GDF-15 expression with muscle mass and exercise performance. To determine whether GDF-15 had a direct effect on muscle, we also determined the effect of increased GDF-15 expression on the tibialis anterior of mice by electroporation. Results Growth differentiation factor-15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF-15 was inversely correlated with rectus femoris cross-sectional area (P

BACKGROUND AND OBJECTIVE: Quadriceps weakness is seen across all GOLD stages of COPD and is associated with increased morbidity and mortality. As quadriceps weakness is only weakly associated with FEV1 , mechanisms other than airflow obstruction are implicated. We tested the hypothesis that insulin resistance contributes to skeletal muscle weakness in people with stable COPD. METHODS: Fifty-one COPD patients (no exacerbations preceding 6 weeks, no rehabilitation preceding 3 months) without known diabetes mellitus underwent assessment of skeletal muscle, including measurement of quadriceps maximal voluntary contraction (QMVC). Physical activity was measured for 7 days using a multisensory biaxial accelerometer armband. Insulin resistance (HOMA2 IR) was calculated from fasting blood glucose and insulin concentrations. RESULTS: QMVC was 30 ± 13 kg (74 ± 25% predicted) and 16 (31%) participants had quadriceps weakness. There was a negative univariate correlation between HOMA2 IR and QMVC (r = -0.446, P = 0.002). HOMA2 IR was greater in people with quadriceps weakness (1.59 ± 0.99) than in those without (1.11 ± 0.55, P = 0.032). On multivariate analysis, with age, sex, weight, BODE index and step count per day included in the model, a one-unit increase in insulin resistance was associated with a 5.9 (2.0-9.8)-kg decrease in QMVC (P = 0.004) and a 4.2 (1.3-14.3)-fold increased risk of quadriceps weakness (P = 0.02). CONCLUSION: Insulin resistance is associated with skeletal muscle weakness in COPD, independent of potential confounders. Further studies are required to explore underlying mechanisms and determine whether insulin-sensitizing drugs could augment pulmonary rehabilitation in building skeletal muscle strength in COPD.

Background COPD is linked to risk of MI, stroke and white matter brain lesions, but there is no recognised method of identifying those who go on to have acute vascular events. It also remains unclear if vascular risk in COPD is truly independent of smoking. The Novel Vascular Manifestations of COPD (NoVasC) study was designed to address this limitation through direct comparison of COPD patients and smoking controls using multimodal brain MRI, retinal photography, cardiac MRI (CMR) and aortic stiffness in addition to cognitive and disease severity measures. Methods MR brain volumes, diffusion, blood flow and white matter lesions were acquired for 27 COPD patients (age 67±8, 41% male, pack years 39±21, FEV158%±18% predicted) and 23 controls (age 63±9, 48% male, pack years 30±14, FEV1101%±19% predicted). CMR of LV and RV function, volumes and aortic distensibility were captured using a 3-Telsa MR scanner. Pulse wave velocity and augmentation index were acquired using Vicorder. Retinal fundus photographs were analysed using validated automated software (SIVA). Analyses adjusted for differences in age, gender, blood pressure and pack years smoked. Results Significant differences in grey matter volume (p=0.004), retinal vessels (p=0.005) and CMR (p=0.01) were identified in COPD (Table 1). There was significant correlation between grey matter volume and BMI (r=−0.42 p=0.005) only. White matter lesion volume was associated with FEV1/FVC and creatinine (r=0.29 p=0.048 and r=−0.33 p=0.027). Cerebral blood flow was associated with arterial pH in COPD (r=−0.49 p=0.019).There were no significant associations identified between other MR brain, cognition, disease severity or retinal measures. Significant correlations were identified between CMR and white matter damage (DTI r=0.50 p=0.001) and FEV1/FVC (r=0.447 p=0.003) and retinal measures with FEV1% pred (r=−0.43 p=0.006). Conclusions Grey matter atrophy, retinal vessel dilatation, and aortic distensibility are present in COPD. White matter lesions volume is associated with lung function but there was no relationship between other MRI brain measures, cognition or disease severity. Non-invasive vascular measures of retinal vessels and cardiac MR appear to relate to lung function and white matter damage and warrant further investigation in larger longitudinal studies of vascular events in COPD.

Hospital admissions for exacerbations are major events in the lives of people with COPD. The prognosis for such patients is grim. Around one in seven will die within 3 months of admission, and fewer than half will still be alive at 5 years.1 ,2 The symptoms they experience are frightening and unpleasant,3 their quality of life is reduced4 and the restriction in their physical activity, which may persist for weeks after the onset of symptoms, increases the risk that they will become housebound.5 In comparison with other medical emergencies, such as myocardial infarction and stroke, progress in improving the management of COPD exacerbations has been depressingly slow. Arguably, the last major advance was the introduction of non-invasive ventilation, which took place sometime in the latter part of the last century. Against this backdrop, it is vital that, as a clinical and research community, we should tenaciously pursue all opportunities to improve the experience for these patients. In doing this, we must reflect critically on our existing practice and the pain and burdens it may present for those who endure it. In this issue of Thorax , McKeever et al 6 do just this, by questioning the need for an investigation that many of us would consider almost sacrilegious to omit: the arterial blood gas. Learning and refining the technique of arterial blood sampling is a rite of passage for medical students, junior doctors and increasingly other healthcare professionals. Evidence of their efforts is perhaps most conspicuous among the inpatient COPD population, where masses of haphazardly taped cotton-wool balls adorn the increasingly purpuric wrists of these unfortunate individuals. As McKeever et al have observed, the pain associated with arterial blood …

Physical activity is defined as any body movement made by skeletal muscles that results in energy expenditure, including leisure time, domestic and work-related activities. Patients with COPD are less physically active when compared with people without COPD, including age-matched controls1 and individuals with other chronic illnesses such as heart disease, diabetes and arthritis.2 In fact, physical activity drops off 10 years earlier in patients with COPD than in sedentary healthy people, and before the onset of breathlessness.3 This lack of physical activity is associated with worse health outcomes. Patients with COPD with the lowest levels of physical activity are at increased risk of hospitalisation due to exacerbations4 and of death due to any cause.5 Increasing physical activity therefore has potential to improve health and prolong survival in people with COPD. Furthermore, patients say that an increase in activity is an important goal for them,6 more important than prolonging survival.7 Increasing physical activity however is surprisingly difficult. Pulmonary rehabilitation—a physical and behavioural intervention—improves exercise performance in patients with COPD, but is not always accompanied by increased physical activity in daily life.8 Beyond pulmonary rehabilitation, alternative therapeutic strategies to improve physical activity include counselling, nutritional supplementation, respiratory support and bronchodilators. Recent systematic reviews of such interventions in COPD found that evidence in this field was often low quality and heterogeneous.9 ,10 While interventions targeted at specific patient subgroups appear successful, such as dietary supplementation in cachectic patients and nocturnal non-invasive ventilation with exercise training in hypercapnic patients, …

Hyperglycemia commonly coexists with lung infection and inflammation and these conditions interact to worsen patient outcomes. In patients with acute respiratory infection, neuroendocrine changes and inflammation increase peripheral insulin resistance and hepatic glucose production, causing acute hyperglycemia. Acute hyperglycemia is associated with increased risk of death or prolonged hospital stay in patients with exacerbations of chronic obstructive pulmonary disease (COPD) or pneumonia. Tight control of blood glucose with insulin improves outcomes for patients with critical illness and requires investigation as a treatment strategy for patients with acute respiratory illness outside the intensive care setting. Patients with chronic lung inflammation and infection (COPD and cystic fibrosis) are at increased risk of developing diabetes mellitus. Mechanisms underlying this predisposition in COPD patients include chronic inflammation, which impairs insulin receptor function, and corticosteroid treatment. In cystic fibrosis, the predominant pathology causing diabetes is insulin deficiency due to pancreatic disease. Patients with chronic lung disease and diabetes have increased mortality and accelerated lung function decline compared with those without diabetes. Chronic hyperglycemia may exacerbate chronic lung disease by increasing predisposition to lung infection, by up-regulating inflammation or by causing structural lung damage. Nonpharmacological therapies, including pulmonary rehabilitation and prevention of obesity, both improve outcomes from chronic lung disease and improve glucose tolerance. The possibility of preventing type II diabetes by treating chronic lung inflammation or of slowing pulmonary decline by prevention and treatment of diabetes requires further investigation in randomized controlled trials.

There is a strong comorbid association between COPD and diabetes and linkage to a worsening clinical outcome in COPD. Oxidative stress leads to increased carbonyl stress in COPD as measured by increased levels of reactive carbonyls, levels of which are linked to severity of COPD. In diabetes increased levels of reactive carbonyls results in the formation of Advanced Glycation End Products (AGEs) the formation of which is reversed by an enzyme called Fructosamine-3-Kinase (FN3K). Low levels of expression and activity of this enzyme are linked to a higher incidence of diabetic complications. We therefore investigated the expression levels of FN3K in two separate clinical studies in COPD as this enzyme may be important in controlling the impact of carbonyl stress and possibly disease severity. We found that 83% of healthy subjects expressed FN3K at low levels in airway epithelial cells. In contrast, 75% of smokers exhibited a large significant increase in FN3K expression. Whereas, in COPD patients 67% had low levels of FN3K expression. Metformin treatment of AECOPD patients produced a significant increase (P

Hyperglycaemia is associated with poor outcomes from pneumonia, myocardial infarction and stroke, but the effect of blood glucose on outcomes from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been established. Recent UK guidelines do not comment on measurement or control of blood glucose in AECOPD. A study was therefore undertaken to determine the relationship between blood glucose concentrations, length of stay in hospital, and mortality in patients admitted with AECOPD.Data were retrieved from electronic records for patients admitted with AECOPD with lower respiratory tract infection in 2001-2. The patients were grouped according to blood glucose quartile (group 1,6 mmol/l (n = 69); group 2, 6.0-6.9 mmol/l (n = 69); group 3, 7.0-8.9 mmol/l (n = 75); and group 4,9.0 mmol/l (n = 71)).The relative risk (RR) of death or long inpatient stay was significantly increased in group 3 (RR 1.46, 95% CI 1.05 to 2.02, p = 0.02) and group 4 (RR 1.97, 95% CI 1.33 to 2.92, p0.0001) compared with group 1. For each 1 mmol/l increase in blood glucose the absolute risk of adverse outcomes increased by 15% (95% CI 4 to 27), p = 0.006. The risk of adverse outcomes increased with increasing hyperglycaemia independent of age, sex, a previous diagnosis of diabetes, and COPD severity. Isolation of multiple pathogens and Staphylococcus aureus from sputum also increased with increasing blood glucose.Increasing blood glucose concentrations are associated with adverse clinical outcomes in patients with AECOPD. Tight control of blood glucose reduces mortality in patients in intensive care or following myocardial infarction. A prospective study is now required to determine whether control of blood glucose can also improve outcomes from AECOPD.

Elevated blood glucose is a well recognised and common pathophysiological response to acute illness. The underlying mechanisms include acute increases in hepatic glucose production and peripheral insulin resistance, driven by increases in glucocorticoids, catecholamines and proinflammatory cytokines.1 Acute hyperglycaemia can occur in any acutely unwell patient, irrespective of baseline glucose tolerance, if the illness is sufficiently severe. Acute hyperglycaemia is associated with poor outcomes from a wide range of acute illnesses including myocardial infarction,2 stroke,3 trauma4 and pneumonia.5 The data in relation to hyperglycaemia and acute exacerbations of chronic obstructive pulmonary disease (COPD) are now beginning to emerge. In a previous study, more than 50% patients with acute exacerbations of COPD had random blood glucose ⩾7 mM during their hospital stay.6 This retrospective study could not fully elucidate the relative contributions of acute illness, steroid therapy and underlying diabetes to development of hyperglycaemia. Nevertheless blood glucose ⩾7 mM was significantly associated with increased risk of death or prolonged hospital stay, and the absolute risk of this composite adverse outcome increased by 15% for each 1 mM increase in blood glucose. It is also known that acute hypercapnic respiratory failure is an independent predictor of poor outcome for patients with COPD exacerbations. Non-invasive ventilation (NIV) reduces the likelihood of endotracheal intubation, treatment failure and mortality.7 Moretti and colleagues found that “metabolic complications” of COPD exacerbations, including hyperglycaemia defined as blood glucose >11 mM, were independently associated with “late failure” (>48 h) of NIV after initial success.8 In this study only ∼7% patients had blood glucose >11 mM and the relationship between more moderate hyperglycaemia (>6–11 mM) and outcomes was not determined. Interestingly all of the patients with late NIV failure who had admission blood glucose >11 mM subsequently developed pulmonary infection, which may …

Introduction and objectives Cognitive impairment is a common co-morbidity in chronic obstructive pulmonary disease (COPD) and is associated with poor disease management, greater disability and mortality [Chang et al., J Am Geriatr Soc, 2012;60:1839–46]. We have previously shown that cognitive impairment is worse in COPD patients during and after hospitalisation for exacerbations, than in those with stable disease [Dodd et al. Chest, 2013;144:119–27]. Our aim was to use multimodal brain magnetic resonance imaging (MRI) to compare structural brain abnormalities between hospitalised and stable COPD patients and healthy controls. Methods 23 COPD patients hospitalised for exacerbations within the last year (hospitalised), 17 COPD patients not hospitalised within the last year (stable) and 23 healthy age-matched controls, were recruited. Exclusion criteria included neurological or psychiatric disorders, cerebrovascular disease or hypertension. Cognition was measured using the Montreal Cognitive Assessment. T1-weighted (T1W), diffusion tensor (DTI) and Fluid Attenuated Inversion Recovery (FLAIR) were acquired using a Philips 3T scanner. The following brain indicators were calculated: normalised whole brain and ventricular volumes (scan: T1W, software: SIENAX), white matter microstructural fractional anisotropy and mean diffusivity – compared voxelwise using tract–based spatial statistics (DTI, FSL), and white matter lesion volume (FLAIR, dispunc ). Ethical approval was obtained (15/LO/0425). Results Cognition was clinically impaired in hospitalised COPD (median (IQR); 23.0 (5)) but not in stable patients (27.0 (2)) or controls (28.5 (3)), with a significant difference only between hospitalised patients and controls ( p p = 0.046) and controls ( p = 0.028). Hospitalised and stable COPD patients had widespread significant reductions in fractional anisotropy and increased mean diffusivity throughout the white matter skeleton, compared to controls ( p Conclusions Hospitalised COPD patients have greater cognitive impairment compared to stable COPD and controls with evidence of greater ventricular and white matter lesion volumes and damaged white matter microstructure. Mechanisms behind these neuropathological processes and possible links to observed cognitive dysfunction remain unclear, but may involve ischaemic small-vessel disease.

Introduction: COPD has been associated with increased cardiovascular risk, although the mechanisms for this are still unclear. Proposed theories include increased systemic inflammation and accelerated ageing resulting in arterial stiffness. We aimed to evaluate aortic distensibility using cardiac MRI in patients with COPD compared to an age-matched non COPD, ‘healthy’ smoker control group. Methods we recruited 49 subjects, of which 27 had diagnosis of COPD and FEV1/FVC Results Aortic distensibility was reduced in the COPD patients compared to control (0.0022610 × 10−3 mm Hg −1 vs 0.004337 × 10−3 mm Hg−1, p = 0.003). The distensibility of descending aorta was similar in both groups (p = 0.06). Ejection fraction and biventricular volumes were also similar in the two groups. Univariant analysis demonstrated a significant relationship between ascending aorta distensibility and FEV1/FVC ratio. There was no difference when comparing distensibility with smoking status or number of packs per year. Linear regression demonstrated that the degree of aortic distensibility was directly proportional to FEV1/FVC ratio Conclusion Patients with COPD have significantly increased aortic stiffness measured by cardiac magnetic resonance. This was observed in the presence of normal LV/RV systolic function in both groups. This difference was related to FEV1/FVC, and was independent of smoking. Preserved FEV1/FVC showed more elastic ascending aortas. Reduced aortic distensibility could represent the early phase changes in cardiovascular function but further research is needed.

Introduction People with chronic obstructive pulmonary disease (COPD) have considerable disability and reduced life expectancy, despite current treatments. New medicines are required, but few successfully complete clinical trials and become established in practice. During drug development, understanding the nature and magnitude of benefits relevant to patients and risks they will accept to achieve these is important, particularly where the drug has a narrow therapeutic index. Our aim was to explore patient perceptions of the benefit:risk profile of existing and potential COPD therapies. Methods Our local respiratory patient advisory group meets every 3 months to provide input into research. A focus group completed a conjoint analysis exercise1. Four current (aclidinium, azithromycin, carbocisteine) or potential (drug X) COPD medicines were presented iteratively in pairs (Figure 1), comparing the magnitude of likely benefits (reduced exacerbations, improved overall health) and harms (risk of infection, antibiotic resistance, kidney failure, diabetes). For each pairing, participants indicated which medicine they would choose. Participants also ranked potential benefits (reduced exacerbations, increased survival, increased walking distance) and risks (death, kidney failure, diabetes) of medicines in order of importance and discussed how these should be prioritised. Results 9 male and 9 female COPD patients (age range 66–86 years, median 77 years, GOLD 1–4) and 2 carers took part. When confronted with two treatment options, participants consistently chose the treatment with a better safety profile, even if this meant less clinical benefit. Being able to walk further was the most important benefit (70% participants), over preventing exacerbations (5%) or increasing life expectancy (5%). Kidney failure was selected as the most concerning potential risk (50% participants) over chance of death (10%). A strong theme emerged that quality of life was more important than life expectancy. Conclusions Potential users of new treatments can weigh potential benefits and risks and judge their relative importance. This has potential to improve design of clinical trials, patient participation and development of medicines with real relevance to users. Reference Bridges JF, et al. Conjoint analysis applications in health—a checklist: a report of the ISPOR Good Research Practices for Conjoint Analysis Task Force. Value in Health 2011;14(4):403–13.

Introduction and objectives People with COPD admitted to hospital with exacerbations have multiple co-morbidities, impacting on survival, re-hospitalisation and health status1. Although commonly described, there is no consensus coordinating management of COPD and co-morbidities in time- and resource-limited healthcare. We developed a pragmatic ‘stop-go’ pre-screening tool to streamline co-morbidity assessment and determined its efficacy in predicting co-morbid diagnoses made ad-hoc in COPD patients in the year following hospitalisation. Methods Criteria were developed from NICE guidelines for twelve common COPD co-morbidities (Table). These indicated whether each condition was either not present or already diagnosed and treated (STOP – no further action required) or whether it could be present but undetected or could not be assessed (GO –further action required). Electronic records (all patients) and hospital notes (84 patients) were reviewed for COPD patients admitted with exacerbations 1/9/2014–31/12/14 who survived for the subsequent year. The ‘stop-go’ screening tool was completed from admission data. Ad-hoc identification of new co-morbidities, defined by physician-diagnosis or commencement of new medication, was noted over 1 year follow up. Results 120 patients (53% male, 47% female; age 73 ± 10 years) were included. The “stop-go “screening tool identified 7 ± 2 co-morbidities per patient requiring no action and 5 ± 2 co-morbidities (‘could be present’, 2 ± 1; ‘unable to assess’ 3 ± 3) where further action was required. Information from patient records was generally insufficient to screen for anxiety and depression and lacking for around one quarter of patients for atrial fibrillation, diabetes mellitus and cognitive impairment. During 1 year follow-up, patients developed 0.6 ± 0.9 (range 0–3) new diagnoses from the co-morbidities list. The ‘stop-go’ tool was most effective at predicting ad hoc diagnosis of hypertension, heart failure and osteoporosis (table) and less effective at predicting atrial fibrillation and ischaemic heart disease. Conclusions The ‘stop-go’ pre-screening tool has potential to cut down the number of co-morbidities that need to be assessed in time-limited consultations. This could be improved by inclusion of anxiety and depression scoring, routine ECG and HbA1c. It shows early promise in predicting ad-hoc diagnoses, but now needs to be tested prospectively towards improving systematic and cohesive care provision. Reference Public Health Reviews. 2011;32:451–474.

Introduction Prevalence of coronary artery disease (CAD) in chronic obstructive pulmonary disease (COPD) is 16–53% (Smith and Wrobel. Int J Chron Obstruct Pulmon Dis. 2014;9:871–888), with ~25% COPD patients dying from cardiovascular disease. Diverse studies demonstrate ~2-fold increased risk of CAD in COPD after adjustment for known cardiovascular risk factors. By contrast, in asthma increased CAD risk appears to be restricted to smokers (Colak et al . Am J Respir Crit Care Med. 2015 Apr 27). Our objectives were to investigate the association between airflow limitation and severity of coronary artery atheroma in patients undergoing coronary angiography and to determine the effect of smoking on this relationship. Methods Patients attending for elective coronary angiography March–July 2015 underwent clinical assessment and spirometry prior to the procedure. Coronary artery disease burden was quantified from angiograms using the Gensini score (Needland et al. Am Heart J 164:547–552). A single rater (Professor of Interventional Cardiology), blinded to clinical diagnosis, determined number and severity of lesions. Blinded repeats were performed and ratings compared to clinical reports to ensure reliability. A nonlinear score was assigned to each lesion based on the severity of stenosis and a multiplier applied depending on lesion location in the coronary tree. Lesion scores were summed to derive total score, which was log-transformed for analysis. Results 233 people (age 66 ± 10 years (mean±SD), 69% male) had FEV 1 82 ± 21% predicted, FVC 89 ± 21% predicted, FEV 1 :FVC ratio 73 ± 10%, Gensini median score 14 (IQR 6–33). On univariate analysis (Table 1), FEV 1 and FEV 1 :FVC were significantly and inversely correlated with Gensini score, but Gensini was not significantly associated with smoking status or pack year load. On multivariate analysis, neither airflow limitation nor smoking were significant determinants of Gensini. Conclusions People with more severe airflow limitation have more coronary atheroma, but smoking does not appear to be a direct determinant of this relationship. Shared comorbid disease (e.g. dyslipidaemia) between COPD and CAD may be more important than smoking in determining the association, supporting the hypothesis that COPD and CAD are part of a multi-morbid disease complex. References 1 Smith MC, Wrobel JP. Epidemiology and clinical impact of major comorbidities in patients with COPD. Int J Chron Obstruct Pulmon Dis . 2014; 9 :871–88 2 Colak Y, Afzal S, Nordestgaard BG, et al. Characteristics and prognosis of never-smokers and smokers with asthma in the copenhagen general population study. a prospective cohort study. Am J Respir Crit Care Med . 2015; 192 :172–81 3 Neeland IJ, Patel RS, Eshtehardi P, et al. Coronary angiographic scoring systems: an evaluation of their equivalence and validity. Am Heart J 2012; 164 :547–552.e1

Introduction Coronary artery disease (CAD) affects 16–53% people with chronic obstructive pulmonary disease (COPD) and is the cause of death in ~25% (Smith and Wrobel. Int J COPD. 2014;9:871–888). People with COPD have both high prevalence of cardiovascular risk factors and increased systemic inflammation and oxidative stress that can drive atherosclerosis. We therefore tested the hypothesis that patients with COPD have more extensive coronary artery disease compared to those without. Methods All patients attending for elective coronary angiography March–July 2015 were invited to take part in a cross-sectional, observational study. Participants who gave consent underwent clinical assessment and spirometry prior to the procedure. COPD was defined as FEV 1 /FVC 10 pack-year smoking history. CAD burden was quantified from the angiogram using the Gensini score (Neeland et al . Am Heart J 2012;164:547–552). A single rater (Professor of Interventional Cardiology), blinded to clinical diagnosis, determined number and severity of lesions. Blinded repeats were performed and ratings compared to clinical reports to ensure reliability. A nonlinear score was assigned to each lesion based on severity of stenosis and a multiplier applied depending on lesion location in the coronary tree. Lesion scores were summed to derive Gensini score which was log-transformed for analysis. Results 249 of 294 (85%) people approached took part, 46 (19%) had COPD. The Table 1 compares demographic, respiratory disease-related and cardiovascular risk factors between people with and without COPD. Gensini score was higher in COPD patients (22.5 (8.5–46.0)) than in those without (12.5 (6.0–26.8), p = 0.04), indicating greater burden of coronary atheroma. COPD patients had more circumflex lesions and tended to have more lesions in the right coronary artery and in total than those without. Conclusions People with COPD have more severe coronary artery disease than those without. This analysis cannot determine whether this was due to the presence of COPD or the fact that patients with CAD and COPD had much greater cigarette smoke exposure than CAD patients without COPD.

Background Despite currently available treatment, 13.9% of patients admitted to hospital for exacerbations of chronic obstructive pulmonary disease (COPD) die within 3 months, and fewer than half survive 5 years. Most of the cost of COPD to the UK health service, which approaches £1bn/year, is associated with the treatment of exacerbations. There is clearly a need to improve outcomes of patients admitted to hospital for exacerbations, and yet relatively few research studies attempt to recruit patients specifically during this phase of their illness. Methods During 2010–2011, two studies were conducted within our institution recruiting patients hospitalised for COPD exacerbations. One was an observational study with relatively broad entry criteria; the other was a randomised, controlled, interventional trial with more stringent entry criteria (ISRCTN66148745). We analysed the screening logs to identify eligibility rates and potential barriers to recruitment, and to provide a guide for researchers on the feasibility of proposed studies in similar populations elsewhere. Results In the 12-month period commencing March 2010, 172 patients were screened for entry to the observational study. In the period January to June 2011, a further 72 patients, not included in the first study, were screened for entry into the clinical trial. Significant exclusion criteria for each study protocol for were identified; for comparison, these are represented across organ systems (Abstract P216 table 1). 29% of those screened for the observational study were eligible for inclusion and 11% for the clinical trial. The clinical trial identified more renal and metabolic conditions, reflecting their particular relevance to experimental drug administration. The observational study identified more physical factors, such as frailty, which may limit patients9 ability to engage with observational research tasks. Conclusion Patients hospitalised for COPD exacerbations are heterogeneous and have significant and diverse co-morbidities which may limit their eligibility for research studies. In view of this, broad entry criteria are necessary to ensure that studies in this population are feasible. With careful design, such studies will be pivotal in driving improved treatment and outcomes among these patients who, despite their poor prognosis, presently receive disproportionately little research attention.

Measurement of pulmonary leukocyte margination could be a useful biomarker of lung inflammation in COPD, but analysis is complicated by recirculation of labeled leukocytes. 15 minutes of planar nuclear images were obtained after injecting autologous 99mTc-labeled leukocytes in 4 never-smoked controls, 6 stable mild/moderate and 2 exacerbating COPD patients. COPD patients were also imaged for 10 minutes after in vivo red blood cell (RBC) labeling with 99mTc and were re-imaged 2 weeks later to determine reproducibility. Activity as a function of time was measured in regions of interest over lungs and heart. A multi-compartment mathematical model was used to correct for recirculation but failed to provide a biomarker that clearly separated controls from COPD. A simpler model for activity in lungs and heart as a function of time (A(t)) was applied only to time points before recirculation: [A(t) = X1 x (1-exp(-X2 x t)) x exp(-X3 x t), where Xi are adjusted to match the data]. The ratio (R) of X3 (downslope of curve) in the lungs to X3 in the heart was investigated as a biomarker of margination. Values of R were reasonable (1.06±0.08 (SE)) for RBC (i.e. no margination) and 0.76±0.10 for controls (25% margination). In stable COPD patients R was significantly smaller (0.19±0.09, p

Background In tertiary care, bronchiectasis (BE) patients are a highly selected group, often with a complex aetiology or associated disease. The national British Thoracic Society bronchiectasis audit provided us with an opportunity to characterise our secondary care bronchiectasis population. We hypothesised that the majority of bronchiectasis seen in our non-specialist service would be associated with chronic obstructive pulmonary disease (COPD). We therefore determined the prevalence of COPD/BE and compared investigation and management of COPD/BE patients to those with bronchiectasis alone. Methods Patients with a clinical diagnosis of bronchiectasis were identified in respiratory outpatients between 1st October and 30th November 2011 during the national bronchiectasis audit period. Those with bronchiectasis confirmed on CT thorax were included. Data including aetiology, lung function and other investigations were retrieved from electronic records. Results Forty seven patients were identified, age 65±17 years (range 19 to 88 years), 57% female. Forty percent (19) had COPD Other common aetiologies were post-infection (26%), asthma (21%) and idiopathic (11%). The table compares characteristics between bronchiectasis patients with and without COPD. COPD/BE patients were older and had a significantly greater pack year smoking history. Similar investigations were performed in the two groups. COPD/BE patients had significantly worse airflow obstruction and gas transfer than bronchiectasis patients without COPD COPD/BE patients were more likely to have Pseudomonas aeruginosa , Methicillin Resistant Staphylococcus aureus or coliforms cultured from sputum, but antibiotic treatment and prophylaxis was similar in the two groups. Other medications were similar in the two groups, although COPD/BE patients were more likely than those without COPD to be prescribed long acting anti-cholinergic medication. Conclusion In our secondary care setting, COPD is the most common underlying condition associated with bronchiectasis. COPD/BE patients share many clinical characteristics with other bronchiectasis patients and have worse lung function and more pathogenic microorganisms isolated from sputum culture. The emerging association between COPD and bronchiectasis requires further research to improve the characterisation and management of this patient group.

Introduction and Objectives Non-CF bronchiectasis is defined as ‘symptoms of persistent or recurrent bronchial sepsis related to irreversibly damaged and dilated bronchi’ [BTS guidelines 2010]. Radiographic evidence of ‘damaged and dilated bronchi’ can be seen on CT Thorax in up to 50% of COPD patients. However the contribution of radiographic bronchiectasis to the clinical course of COPD is not fully understood. We aimed to determine the impact of bronchiectasis on lung function, sputum microbiology and outcomes in COPD patients, independent of coexisting emphysema and bronchial wall thickening (BWT). Methods COPD patients admitted with first exacerbation 1998–2008 were identified retrospectively using ICD10 codes J44.0,1,8,9. Patients with high resolution CT images within 2 years of admission were included. CT scans were graded by consensus of 2 senior thoracic radiologists for severity of bronchiectasis, emphysema and BWT on a 5 point scale (0-absent, 1-minor, 2-mild, 3-moderate, 4-severe). Operational definitions were set prior to scan review and radiologists were blinded to clinical parameters. Results 406 patients (71±11years, 56% male, FEV1 52±23% predicted) were included. 278 (69%) patients had bronchiectasis: minor, 112 (40%); mild, 81 (29%); moderate, 62 (22%); severe 23 (8%). There was considerable overlap between bronchiectasis and other pathologies (figure). Bronchiectasis severity correlated with severity of BWT (r=0.276, p Pseudomonas aeruginosa (Odds ratio (OR) 1.39 (95% CI 1.07–1.80), p=0.013) and atypical mycobacteria from sputum cultures (OR 2.44 (95% CI 1.04–5.69), p=0.040). After correction for increasing severity emphysema, BWT, age, gender and comorbidities, increasing severity bronchiectasis determined annual admissions (regression coefficient B=0.14 (95% CI 0.00–0.28), p=0.044) and inpatient days (B=2.1 (95% CI 0.8–3.4), p=0.001) for respiratory causes, but did not influence survival from first hospital admission (p=0.257). Conclusions Radiographic bronchiectasis in COPD patients is associated with increased respiratory infection and hospitalisation, independent of coexisting emphysema and BWT. COPD-related bronchiectasis is therefore a diagnosis with important clinical implications. Further research should determine whether treatment strategies for non-CF bronchiectasis can improve the clinical course of COPD-related bronchiectasis.

Background Approximately 10% of patients with chronic obstructive pulmonary disease (COPD) have co-existing diabetes mellitus, conferring an adverse prognosis. Metformin is a valuable first-line treatment for diabetes. However, its rare association with lactic acidosis limits its use among patients at risk of hypoxia. This may deter some practitioners from prescribing it to patients with significant co-existing COPD. It is unknown whether the benefits of metformin outweigh its risks in this context. We therefore sought to determine the effects of metformin on survival and length of stay in a high-risk cohort of diabetic patients hospitalised for COPD exacerbations. Methods The medical records of diabetic patients hospitalised for COPD were reviewed retrospectively. Length of hospital stay and all-cause mortality were compared according to the presence or absence of metformin therapy. Results 130 patients were included, of whom 51 (39%) were prescribed metformin. Patients on metformin had a shorter hospital stay (median 7 vs 9 days respectively; p=0.004). Survival at 90 days was significantly better in the metformin group than in the non-metformin group (94% vs 78% respectively; p=0.015; Abstract P259 figure 1 inset). This persisted over the longer term, with overall median (95% CI) survival of 5.2 years (4.3 to 6.1) in the metformin group and 2.2 years (1.0 to 3.3) in the non-metformin group (HR 0.57; 95% CI 0.35 to 0.94; Abstract P259 figure 1). This difference remained significant in a multivariate model, adjusting for potential confounding effects of age, weight, acute illness severity (APACHE-II score) and comorbidity burden. Among patients prescribed metformin, vs those not, the median (IQR) plasma lactate concentration was 1.45 mmol/l (1.10–2.05) vs 1.10 mmol/l (0.80–1.50), respectively (p=0.012). Conclusion Diabetic patients hospitalised for COPD exacerbations who were prescribed metformin were discharged earlier and survived longer than those not prescribed metformin. Lactate concentration was higher among patients on metformin, although the difference was small. Our results suggest that the drug9s benefits may outweigh its rare association with lactic acidosis. Whether this reflects beneficial effects on diabetes- or COPD-related endpoints; other associated conditions; or the effect of unmeasured confounders, is unknown. We are now investigating this within the context of a randomised controlled trial (ISRCTN66148745).

Background Hyperglycaemia is associated with poor outcomes from exacerbations of chronic obstructive pulmonary disease (COPD). Glycaemic control could improve outcomes by reducing infection, inflammation and myopathy. Most patients with COPD are managed on the acute medical unit (AMU) outside intensive care (ICU). Objective To determine the feasibility, safety and efficacy of tight glycaemic control in patients on an AMU. Design Prospective, non-randomised, phase II, single-arm study of tight glycaemic control in COPD patients with acute exacerbations and hyperglycaemia admitted to the AMU. Participants received intravenous, then subcutaneous, insulin to control blood glucose to 4.4–6.5 mmol/l. Tight glycaemic control was evaluated: feasibility, protocol adherence; acceptability, patient questionnaire; safety, frequency of hypoglycaemia (capillary blood glucose (CBG), Article summary Article focus Hyperglycaemia is associated with poor outcomes from acute chronic obstructive pulmonary disease (COPD) exacerbations requiring hospital admission. It is not known whether glycaemic control can improve COPD exacerbation outcomes. The aim of this phase II study was to determine the feasibility, safety and efficacy of tight glycaemic control with insulin in COPD patients with exacerbations on acute medical wards, towards testing this intervention in a randomised controlled trial. Key messages Tight glycaemic control with insulin was feasible and acceptable to patients in a general ward setting. The efficacy and safety of tight glycaemic control were similar in COPD patients on acute medical wards to that achieved in intensive care settings, with improved glycaemic control but increased hypoglycaemia and glycaemic variability. Strengths and limitations of this study This study was conducted when tight glycaemic control was standard practice in intensive care units (ICUs), following the publication of two single-centre studies demonstrating reduced morbidity and mortality compared with conventional glycaemic control. More recent ICU studies have shown no benefit and possible harm from tight glycaemic control. In this context, our finding that tight glycaemic control in the acute medical unit has a similar safety and efficacy to ICU protocols indicates that we should explore alternative strategies for blood glucose control in COPD exacerbations.