Introduction: Early use of anti-fibrotic medication in pulmonary fibrosis protects lung function, prolonging quality of life. Increased use of CT could enable detection of disease before significant symptoms develop. The majority of CT scans are requested by primary care teams, general physicians or surgeons. However these groups are unfamiliar with the significance of classical descriptors for pulmonary fibrosis used by radiologists. A recent case (patient presented with disabling breathlessness requiring oxygen at diagnosis, a year after CT for cholecystitis) led us to audit our ILD clinic with the aim of determining local prevalence. Methods: 116 patient records at a University Clinic were reviewed, to ascertain the prevalence of CT abdomen scans prior to referral. In addition to reports with 'refer to respiratory' we sought words commonly employed to describe fibrosing interstitial lung diseases (reticulation, honeycombing, ground glass). Findings 11 patients had abdominal CT scans before referral. 5 had fibrosis present. Time from these scans to clinic review ranged from 3 to 36 months. Only 2 reports recommended referral to the respiratory team. A further 2 contained descriptors but no guidance, and one report failed to describe the fibrosis. Reports recommending 'refer to respiratory' were followed. Of the remaining three patients, all were referred by their GP following presentation with symptoms. Conclusions: Abdominal CTs could enable early referral to ILD clinics, but this opportunity is lost due to reporting habits. Clear guidance to requestors is followed and should be employed as standard. Radiology training and education should target this issue, to improve outcomes for patients.

While research on the effects of computers in classrooms and the effects of teaching computer languages is burgeoning, the question of how children interact "naturally" with a computer has not been researched. In order to observe children's interaction with a computer, an Apple II was placed in a university laboratory school classroom. Thirty-nine children were allowed free access to the computer during center time and detailed observational logs were kept of the children's interaction with the computer. It was determined from this base study that computer play for young children is an initial step in computer literacy.

Fractional exhaled nitric oxide (FeNO) is the only available point of care test to assess type-2 inflammation in asthma. In making a diagnosis of asthma, FeNO should be used together with blood eosinophils and spirometry, alongside a history. Raised FeNO in conjunction with blood eosinophilia are treatable traits of type 2 inflammation in asthma, which in turn may guide personalised management. A FeNO suppression test can be used to assess adherence and device use with ICS therapy. Furthermore FeNO may be used to provide feedback to patients in response to ICS, especially when spirometry is normal. FeNO may facilitate appropriate referral to secondary care for more definitive specialist investigations. In summary, FeNO is cost effective in the diagnosis and management of asthma and should be incorporated into primary and secondary care as part of routine clinical practice.

This study compares the in vivo relative lung bioavailability of Hydrofluoroalkane (HFA) Seretide delivered via unprimed and unwashed Aerochamber Plus (AP) or Volumatic (VM) spacers, a integrated breath-actuated vortex Synchro-Breathe (SB) device and an Evohaler pMDI (EH) device using adrenal suppression and early fall in serum potassium (K) as surrogates for respirable dose.Seventeen healthy volunteers completed this randomised double-blind, double-dummy crossover study. Single doses of placebo/Seretide 250 (total dose ex valve fluticasone 2000 mcg/salmeterol 200 mcg) were administered via the devices. Overnight urinary cortisol/creatinine (OUCC) and serum K were measured at baseline and after each dose.Significant suppression of OUCC and K occurred from baseline with the SB, AP and VM but not with the EH devices. The geometric mean fold suppression (95% confidence interval, p) was: EH, 1.59 (0.80-3.14, p = 0.40); AP, 4.26 (3.01-6.02, p < 0.001); VM, 3.11 (1.99-4.78, p < 0. 001); SB, 3.29 (2.04-5.24, p < 0.001). For K, the arithmetic mean fall (mmol/l) (95% confidence interval; p) was: EH, -0.10 (-0.25-0.05, p = 0.18); AP, -0.23 (-0.41 to -0.04, p = 0.02); VM, -0.22 (-0.44 to -0.01, p = 0.04); SB, -0.28 (-0.42 to -0.13, p = 0.001).The breath-actuated SB device was comparable to 'out of the box' small and large volume spacers and produced similar improvements in relative systemic lung bioavailability for fluticasone and salmeterol.

Background: The murine asthma model shows that switching off airway beta-2 receptors with an inverse agonist may confer anti-inflammatory as well as steroid-sparing activity. We therefore assessed the putative steroid sparing effects of propranolol, an inverse agonist, by comparing propranolol plus low-dose inhaled corticosteroid (ICS) vs. higher dose ICS alone. Methods: Randomised, double blind, placebo-controlled, crossover trial in mild-moderate persistent asthmatics. Run-in (2weeks): HFA-BDP 100μg/day. Randomised treatments (4weeks): propranolol 80mg/day + HFA-BDP 100μg/day; versus placebo + HFA-BDP 400μg/day. Propranolol up-titrated to 80mg/day over initial 2weeks. Tiotropium co-administered until 5 days pre-histamine challenge (primary outcome). Results: 16 patients completed, mean: age 38yr; FEV 1 86·4%; Histamine PC 20 1·39mg/ml; ICS 406μg/day. Histamine PC 20 remained unchanged with propranolol + HFA-BDP100 compared to baseline (HFA-BDP100): 0·17 doubling dilution (dd) difference (95%CI -0·58-0·92). There was a significant improvement with HFA-BDP400 vs. baseline: 1·05dd (95%CI 0·43-1·66), P=0·02; and vs. propranolol + HFA-BDP100: 0·88dd (95%CI 0·45-1·30), P=0·006. Significant improvements occurred with HFA-BDP400 vs propranolol + HFA-BDP100 for FeNO, Eosinophils and ECP, and for AQLQ symptom score. Evening FEV 1 fell with propranolol: 0·22L (95%CI 0·10-0·34L), P=0·012, while ACQ and AQLQ remained unchanged. Conclusion: The inverse agonist propranolol produced no improvements when added to low dose ICS, while further significant improvements in AHR and inflammation were demonstrated with higher dose ICS. Thus propranolol does not confer steroid-sparing activity in persistent asthma.

The murine asthma model shows that switching off airway β2 receptors with an inverse agonist may confer anti-inflammatory effects as well as corticosteroid-sparing activity. We have assessed for any corticosteroid-sparing effects of propranolol, an inverse agonist, added to low-dose inhaled corticosteroid (ICS) compared with higher dose ICS. A randomized double-blind placebo-controlled cross-over trial in mild-to-moderate persistent asthmatic patients was performed. After a run-in (2 weeks) on hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) at 100 μg/day (HFA-BDP100), patients received randomized treatments (4 weeks) with propranolol at 80 mg/day plus HFA-BDP at 100 μg/day compared with placebo plus HFA-BDP at 400 μg/day (HFA-BDP400). Propranolol was up-titrated to 80 mg/day over the initial 2 weeks. Tiotropium was co-administered until 5 days before each histamine challenge (the primary outcome). Sixteen patients completed the study [mean age, 38 years; forced expiratory volume in 1 s (FEV1), 86.4%; histamine provocative concentration causing a 20% fall in FEV1 (PC20), 1.39 mg/ml; ICS dose, 406 μg/day]. Histamine PC20 was unchanged by adding propranolol to HFA-BDP100 compared with baseline (HFA-BDP100) {0.17 doubling dilution (dd) difference [95% confidence interval (CI): -0.58 to 0.92]}, but there was a significant improvement with HFA-BDP400 compared with both baseline [1.05 dd (95% CI: 0.43-1.66); P=0.02], and propranolol+HFA-BDP100 [0.88 dd (95% CI: 0.45-1.30); P=0.006]. Significant improvements were also observed with HFA-BDP400 for exhaled nitric oxide, blood eosinophils, serum eosinophilic cationic protein and asthma quality-of-life questionnaire symptoms compared with propranolol+HFA-BDP100. Salbutamol recovery post-challenge was partially blunted by propranolol (median prolongation 5 min; P=0.002). Domiciliary evening FEV1 also fell with propranolol+HFA-BDP100 [mean reduction from baseline 0.22 litres (95% CI: 0.10-0.34); P=0.012], whereas Asthma Control Questionnaire remained unchanged. In conclusion, the inverse agonist propranolol produced no improvements when given with low-dose ICS, whereas further significant improvements in airway hyper-responsiveness and inflammation were demonstrated with higher dose ICS. Thus, propranolol does not confer corticosteroid-sparing activity in persistent asthma.

OBJECTIVE:Despite their benefits in the treatment of cardiovascular disease, β-blockers are seldom used to treat asthmatics. We assessed the safety and tolerability of acute dosing with esmolol and propranolol in patients with asthma. DESIGN:Post-hoc analysis of a double blind, randomised, placebo controlled trial of β-blocker use in asthma. PATIENTS:Mild-to-moderate asthmatics on inhaled corticosteroids. INTERVENTIONS:Each participant underwent a 6-8 week dose titration of oral propranolol. A subgroup received an intravenous bolus dose of esmolol (0.5 mg/kg). Measurements were recorded pre- and post-esmolol and first dose exposure to 10 mg, 20 mg, and 80 mg of propranolol. Tiotropium was given concurrently with propranolol. Bronchoconstriction was reflected as a fall in forced expiratory volume in 1 s (FEV1) or increase in total airway resistance at 5 Hz (R5). RESULTS:12 patients completed the trial. There were no adverse effects on FEV1% or R5% following intravenous esmolol. There were significant reductions at 2 min post-esmolol in heart rate (-4.7 beats/min (bpm), 95% CI -7.9 to -1.3 bpm; p=0.002) and systolic blood pressure (-5.9 mm Hg, 95% CI -11.4 to -0.4 mm Hg; p=0.03). No bronchoconstriction was seen during up titration following the first dose of 10 mg, 20 mg or 80 mg of propranolol in the presence of tiotropium. No difference in the asthma control questionnaire at 80 mg propranolol was seen versus placebo in the presence of tiotropium. CONCLUSIONS:Intravenous esmolol was administered without any adverse effects on pulmonary function in selected, stable, mild-to-moderate asthmatics controlled on inhaled corticosteroids. Tiotropium prevented propranolol induced bronchoconstriction after acute dosing during up-titration to 80 mg with no adverse impact on asthma control.

Introduction: Bronchiectasis is common in severe COPD, but its impact on outcomes after exacerbations of COPD has not been reported. Methods: Analysis was performed on a prospective multicentre observational database of patients hospitalised in the UK with exacerbations of COPD (2009-2011). Patients with co-existing bronchiectasis were compared to those with COPD. Outcomes were assessed adjusting for confounders using cox-proportional hazard regression. Results: Of 1343 patients, 136 had a co-existing diagnosis of bronchiectasis. Baseline demographics between the groups were similar (Table 1). Patients with bronchiectasis had significantly increased 30-day mortality hazard ratio (HR) 2.2 95% CI 1.1-4.3,p=0.03, despite a higher proportion with acidosis in the non-bronchiectasis group. Patients with bronchiectasis had a higher positive yield for microbiology and an appropriately prolonged antibiotic course. After discharge, patients with bronchiectasis had an increased risk of readmission HR 1.5 (1.03-2.2,p=0.03) and particularly respiratory readmissions HR 1.9 (1.1-3.2,p=0.01). 1 year mortality was not significantly increased HR 1.4 (0.98-1.9,p=0.06). Conclusion: Bronchiectasis is associated with higher in-hospital mortality and a higher risk of readmissions after discharge in patients with exacerbation of COPD.

Introduction We compared GOLD 2007 and 2011 stratification, assessing their ability to predict mortality and hospital admissions in two distinct COPD populations across a spectrum of COPD severity. Methods A prospective multi-centre dataset of patients hospitalised with COPD exacerbations (EXODUS) and a large retrospective community cohort of COPD patients (TARDIS) were used. Analyses were performed independently. Patients were stratified by GOLD 2007 and 2011. Kaplan Meier with log-rank testing and the C-statistic were used. Results EXODUS: 1261 patients, median (IQR) FEV1% 48.6%(34.2-67.2), 1 year follow up. TARDIS: 3293 patients, median (IQR) 61.2%(33.8-88.6), mean follow up 4.7 years. Increasing GOLD 2007 stage correlated with reduced survival within both datasets, (Log rank test p C-statistics showed GOLD 2011 staging to have a better predictive ability for mortality than GOLD 2007 in both datasets; EXODUS AUC 0.62 (0.59-0.64) for GOLD 2011 vs. AUC 0.55 (0.53-0.57) for GOLD 2007, TARDIS AUC 0.65 (0.64-0.66) for GOLD 2011 vs AUC 0.61 (0.60-0.62) for GOLD 2007. For hospital readmissions, with TARDIS, GOLD 2011 had a better predictive ability than GOLD 2007. Within EXODUS, GOLD 2011 was equivalent to GOLD 2007. Conclusions GOLD 2011 identifies patients at risk of future death and hospitalisation more accurately than spirometry alone.

Background The effect of hyperglycaemia on outcome following acute exacerbation of COPD (AECOPD) is unclear and may be confounded by several factors including comorbid diabetes mellitus (DM) and prior oral corticosteroid (OCS) use. The aim of this study was to evaluate the effect of hyperglycaemia and DM on short and long-term outcomes following hospitalised AECOPD. Methods We conducted a multi-centre prospective observational study assessing patients hospitalized with AECOPD. All patients had serum glucose measured on admission. Outcomes of interest were 30 day and 1 year mortality. Results There were 1069 patients included. Diabetes was significantly more frequent in the moderate and severe hyperglycaemia groups but there was no significant difference in OCS use prior to admission. Table 1 shows 30 day mortality according to glycaemic level, adjusted for a number of potential confounders including OCS use, in all patients and in non-diabetics. Hyperglycaemia was not significantly associated with any alteration in 1 year mortality but comorbid DM was associated with significantly reduced 1 year mortality (HR 0.68 (0.46-0.97); p=0.047). Conclusion Severe hyperglycaemia is associated with increased short-term mortality following AECOPD independently of comorbid DM and prior OCS use. Comorbid DM is associated with improved long-term outcome.

Background: Asthmatic patients receiving inhaled corticosteroids (ICS) may take frequent add-on short acting beta agonist (SABA) despite on-demand prescription. B2-adrenoceptor (B2ADR) genotype 16 may influence this. Methods: A randomised double-blind triple crossover study comparing 2 weeks regular inhaled racemic salbutamol (200µg qid); levosalbutamol (100µg qid); or placebo on diurnal PEF and 6h trough methacholine PC20 in 30 persistent asthmatics (15 homozygous Arg16 and Gly16) all receiving ICS. Results: Active SABAs improved evening PEF in both Gly16 (p<0.001) and Arg16 patients (p=0.006); morning PEF did not improve with either SABA in Arg16 patients (p=0.5) compared to improvement in Gly16 patients (p=0.04) ![Figure][1] There was no worsening of airway hyper-responsiveness (AHR) at trough to methacholine after 2 weeks regular exposure to either racemic (p=0.53) or levosalbutamol (p=0.84) compared to placebo; nor between genotypes as doubling dilution (dd) difference in methacholine PC20 from placebo. Conclusion: B2ADR genotype 16 influenced differential improvements in morning pre-bronchodilator PEF when using regular SABA in addition to ICS. There was no worsening of trough AHR at 2 weeks by genotype or active SABA compared to placebo. [1]: pending:yes

Objective To study the association of clarithromycin with cardiovascular events in the setting of acute exacerbations of chronic obstructive pulmonary disease and community acquired pneumonia. Design Analysis of two prospectively collected datasets. Setting Chronic obstructive pulmonary disease dataset including patients admitted to one of 12 hospitals around the United Kingdom between 2009 and 2011; Edinburgh pneumonia study cohort including patients admitted to NHS Lothian Hospitals between 2005 and 2009. Population 1343 patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease and 1631 patients admitted with community acquired pneumonia. Main outcome measures Hazard ratios for cardiovascular events at one year (defined as hospital admissions with acute coronary syndrome, decompensated cardiac failure, serious arrhythmia, or sudden cardiac death) and admissions for acute coronary syndrome (acute ST elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina). Secondary outcomes were all cause and cardiovascular mortality at one year. Results 268 cardiovascular events occurred in the acute exacerbations of chronic obstructive pulmonary disease cohort and 171 in the community acquired pneumonia cohort over one year. After multivariable adjustment, clarithromycin use in acute exacerbations of chronic obstructive pulmonary disease was associated with an increased risk of cardiovascular events and acute coronary syndrome—hazard ratios 1.50 (95% confidence interval 1.13 to 1.97) and 1.67 (1.04 to 2.68). After multivariable adjustment, clarithromycin use in community acquired pneumonia was associated with increased risk of cardiovascular events (hazard ratio 1.68, 1.18 to 2.38) but not acute coronary syndrome (1.65, 0.97 to 2.80). The association between clarithromycin use and cardiovascular events persisted after matching for the propensity to receive clarithromycin. A significant association was found between clarithromycin use and cardiovascular mortality (adjusted hazard ratio 1.52, 1.02 to 2.26) but not all cause mortality (1.16, 0.90 to 1.51) in acute exacerbations of chronic obstructive pulmonary disease. No association was found between clarithromycin use in community acquired pneumonia and all cause mortality or cardiovascular mortality. Longer durations of clarithromycin use were associated with more cardiovascular events. Use of β lactam antibiotics or doxycycline was not associated with increased cardiovascular events in patients with acute exacerbations of chronic obstructive pulmonary disease, suggesting an effect specific to clarithromycin. Conclusions The use of clarithromycin in the setting of acute exacerbations of chronic obstructive pulmonary disease or community acquired pneumonia may be associated with increased cardiovascular events. These findings require confirmation in other datasets.

Objectives Unblinded studies have shown improvements in airway hyper-responsiveness (AHR) with chronic nadolol in steroid naive asthmatics. To assess the effects of chronic non selective beta-blockade as add on to inhaled corticosteroids (ICS) in asthmatics. Methods A double-blind randomised placebo controlled crossover trial of propranolol in mild-to-moderate asthmatics receiving ICS was performed. Participants underwent a six to eight week dose titration of propranolol or placebo as tolerated to a maximum of 80mg per day. Tiotropium was given for the first four to six weeks of each treatment period. Primary outcome was methacholine challenge. Secondary outcomes included histamine challenge, pulmonary function, mini-asthma quality of life questionnaire (mini-AQLQ) and asthma control questionnaire (ACQ). Results 18 patients completed: mean (SEM); age 36 (4), FEV1% 93 (2), ICS ug/day 440 (66). No significant difference was observed in methacholine or histamine challenge following exposure to propranolol versus placebo. For methacholine challenge the doubling dilution difference (DDD) was 0·04 (95%CI -0·56 - 0·63), p=0·89. Salbutamol recovery at 20mins post histamine challenge was partially attenuated by propranolol vs placebo, FEV1% mean difference: 5.28 (95%CI 2.54-8.01), p=0.001. Post chronic beta-blockade there was a small worsening in FEV1 % predicted of 2·4% (95%CI -0·1 - 4·8), p=0·055. No difference was found for ACQ or mini-AQLQ. Conclusions This is the first placebo controlled study to assess the effects of chronic non selective beta-blockade in asthma, showing no significant effect of propranolol compared to placebo on either methacholine or histamine AHR and no change in ACQ or AQLQ.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Extra fine inhaled corticosteroid formulations such as HFA beclomethasone may be used to target the small airways in asthma. However, it is unclear which outcome measures may detect such small airways effects in patients with severe asthma. WHAT THIS STUDY ADDS • The alveolar fraction of exhaled nitric oxide is not a sensitive outcome measure for following effects of extra fine particle inhaled beclomethasone in severe asthma. However there were significant effects on nitric oxide fractions measured at 50 ml s −1 and bronchial flux with the extra fine formulation, which did not produce significant cortisol suppression. AIMS Alveolar nitric oxide (CA NO ) is a potential biomarker of small airway inflammation . We investigated effects on CA NO of the addition of coarse and fine particle inhaled corticosteroids to standard therapy in severe asthma. METHODS Severe asthmatics taking ≥1600 µg day −1 budesonide or equivalent performed a randomized open‐label crossover study. Subjects with FEV 1 < 80%, gas trapping and CA NO ≥2 ppb entered a 6 week dose‐ramp run‐in of fluticasone/salmeterol(FPSM) 250/50 µg twice daily for 3 weeks, then 500/50 µg twice daily for 3 weeks. Patients then received additional HFA‐beclomethasone diproprionate (BDP) 200 µg twice daily or FP 250 µg twice daily for 3 weeks in a crossover. Participants then received prednisolone(PRED) 25 mg day −1 for 1 week. Nitric oxide, lung function, mannitol challenge, systemic inflammatory markers and urinary cortisol were measured. RESULTS Fifteen completed per protocol: mean (SD) age 51 (12) years, FEV 1 58 (13)% predicted, residual volume 193 (100)% predicted and mannitol PD10 177 (2.8) µg. There was no significant difference between FPSM and add‐on therapy for CA NO . FPSM/BDP and FPSM/PRED suppressed broncial flux (Jaw NO ) and FE NO compared with FPSM alone, but there was no significant difference between FPSM/BDP and FPSM/FP. ECP, e‐selectin and ICAM‐1 were suppressed by FPSM/PRED compared with FPSM and FPSM/FP but not FPSM/BDP. Plasma cortisol was significantly suppressed by FPSM/PRED. CONCLUSION In severe asthma, CA NO is insensitive to changes in dose and delivery of inhaled corticosteroids and is not suppressed by systemic corticosteroids. Additional inhaled HFA‐BDP reduced FE NO and Jaw NO without adrenal suppression. There was a trend to reduction in FE NO and Jaw NO with additional FP but this did not reach statistical significance. PRED reduced FE NO and Jaw NO with suppression of systemic inflammatory markers and urinary cortisol.

Objectives We wished to assess the safety and tolerability of acute dosing of both propranolol and esmolol in mild-to-moderate asthmatics. Methods A secondary analysis of a double-blind randomised placebo controlled trial was performed ([NCT01074853][1]). Participants underwent dose titrations of propranolol (10mg BD, 20mg BD, 80mg OD). Prior to randomisation participants received an intravenous bolus dose of esmolol (0.5mg/kg). Spirometry, impulse oscillomtery and heart rate were recorded. For each dose titration of propranolol, tiotropium was given concurrently. Results 12 participants completed: mean (SEM); age 37(5), FEV1% 93 (2), R5% 127 (12), ICS ug/day 390 (67) No significant difference was seen for FEV1% predicted or R5% predicted following esmolol use. ![Figure][2] There were reductions in heart rate, 2 minutes post esmolol, mean difference 4bpm (95%CI 1.2 -7.5). There were significant worsening of FEV1% (mean difference 4.1% (95%CI 0.22 – 7.9) and R5% 38.3% (95%CI 20.5 - 56.1) 45 minutes post 10mg propranolol. Tiotropium prevented any further bronchoconstriction post 45 minutes and also at each subsequent up-titration visit. Conclusions Acute esmolol dosing did not cause any worsening of pulmonary function within our cohort of asthmatics. Acute propranolol dosing caused evidence of bronchoconstriction with a greater signal seen with impulse oscillometry. Tiotropium prevented any further bronchoconstriction at up-titration visits. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01074853&atom=%2Ferj%2F42%2FSuppl_57%2FP3646.atom [2]: pending:yes

Asthmatic patients receiving ICSs (inhaled corticosteroids) may take frequent add-on therapy with salbutamol despite on-demand prescription. Frequent salbutamol use can be detrimental in asthma. The isomeric formulation of salbutamol and the B2ADR (β2 adrenoceptor) 16 genotype may also influence this phenomenon. We performed a randomized, double-blind, placebo-controlled, triple crossover, proof of concept trial comparing 2 weeks of regular therapy with inhaled racemic salbutamol [200 μg q.i.d. (four times daily)], levosalbutamol (100 μg q.i.d.) or placebo on trough methacholine PC20 [provocative concentration causing 20% fall in FEV1 (forced expiratory volume in 1 s)] 6 h post-dose (the primary outcome) in 30 persistent asthmatic patients (15 who were Arg16 homozygous and 15 who were Gly16 homozygous) all receiving ICSs. There was no worsening of AHR (airway hyper-responsiveness) at trough to methacholine after 2 weeks regular exposure to either racemic (P=0.53) or levosalbutamol (P=0.84) compared with placebo, nor between genotypes-as dd (doubling dilution) difference in methacholine PC20 from placebo [salbutamol/Arg16=0.36 dd [95% CI (confidence interval), -0.43, 1.15]; salbutamol/Gly16=0.01 dd (95% CI, -0.47, 0.49); levosalbutamol/Arg16=-0.01 dd (95% CI, -0.89, 0.87); and levosalbutamol/Gly16=0.28 dd (95% CI, -0.22, 0.77)]. Both active treatments improved morning PEF (peak expiratory flow) in Gly16 (P=0.04 overall) but not Arg16 (P=0.50 overall) patients, whereas evening PEF improved in both Gly16 (P<0.001 overall) and Arg16 (P=0.006 overall) patients. In conclusion, the regular exposure to either racemic or levosalbutamol for 2 weeks added to ICSs did not cause worsening of AHR at trough compared with placebo; with no difference seen between B2ADR 16 genotypes.

BackgroundTiotropium has been shown to improve lung function, quality of life, and exacerbations and reduce mortality when compared with placebo in COPD. It remains unclear whether benefits are seen when tiotropium is used in conjunction with inhaled corticosteroids (ICSs) plus long-acting β-agonists (LABAs).MethodsWe performed a retrospective cohort study using a National Health Service database of patients with COPD in Tayside, Scotland, between 2001 and 2010 that is linked with databases regarding hospital admissions, pharmacy prescriptions, and death registries. The impact of the addition of tiotropium (Tio) to ICS + LABA therapy on all-cause mortality, hospital admissions for respiratory disease, and emergency oral corticosteroid bursts was evaluated. Adjusted hazard ratios (HRs) were calculated by Cox regression after inclusion of the following covariates: cardiovascular and respiratory disease, diabetes, smoking, age, sex, and deprivation index.ResultsA total of 1,857 patients were given ICS + LABA + Tio, and 996 were given ICS + LABA. Mean follow-up was 4.65 years. The adjusted HR for all-cause mortality for ICS + LABA + Tio vs ICS + LABA was 0.65 (95% CI, 0.57-0.75; P < .001). Adjusted HRs for hospital admissions and oral corticosteroid bursts were 0.85 (95% CI, 0.73-0.99; P = .04) and 0.71 (95% CI, 0.63-0.80; P < .001), respectively.ConclusionsThe study suggests that the addition of tiotropium to ICSs and LABA therapy may confer benefits in reducing all-cause mortality, hospital admissions, and oral corticosteroid bursts in patients with COPD. Triple therapy is widely used in the real-life management of COPD, with only limited scientific support. The study supports the use of triple therapy in COPD and provides a platform for randomized controlled trials specifically addressing this topic.

Background Antibiotics are frequently used in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. However, international guidelines suggest their use should be restricted to specific sub-groups based on the Anthonisen Criteria. The aim of this study was to assess the impact of antibiotic therapy on outcome in COPD. Methods We conducted a multi-centre prospective observational study assessing patients hospitalized with COPD exacerbation. Multivariable logistic regression was used to compare outcomes in patients treated with and without antibiotic therapy, including adjustment using a propensity score and adjustment for recognised predictors of 30-day mortality. The outcomes of interest were 30-day mortality and length of hospital stay. Results 1031 patients were included in the study. Median age was 74 years (interquartile range 63-75) and 48.7% were female. Mean FEV1 was 46% (standard deviation 19%). 30-day mortality was 5.4%. 818 patients (79.3%) received antibiotic therapy on admission (23.5% combination therapy, 76.5 % monotherapy). Antibiotic prescribing according to Anthonisen criteria was: Type 1 - 84% patients received antibiotics, Type 2 - 78.6% and Type 3 - 70.3%. After adjustment for propensity to receive antibiotic therapy and recognized predictors of mortality, there was no association between antibiotic use and 30 day mortality (OR 0.96 (0.37-2.48), p=0.9) or length of hospital stay (p=0.8). Conclusion Antibiotic treatment is frequently used in hospitalised acute exacerbations of COPD. This study did not find any evidence of benefit in terms of mortality or length of hospital stay.