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BackgroundLongitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma.MethodsWe used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000–31 December 2016) retrospective cohort of reproductive-age (16–45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition.ResultsThe 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3–4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use.ConclusionsUse of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required.Protocol registration numberEuropean Union electronic Register of Post-Authorisation Studies (EUPAS22967).

BackgroundLittle is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study.MethodsThe study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1decline. Effect modification by blood eosinophils was studied through interaction terms.ResultsOf 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1decline of 19.4 mL/year (95% CI 12.0 to 26.7, pConclusionExacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.

BackgroundLittle is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs.AimsWe sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population.MethodsThis cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×109/L) for patients prescribed long-acting β2-agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population.ResultsOf 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1).ConclusionsLess than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma.

OBJECTIVE To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma. DESIGN Cross-sectional observational study. SETTING The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry. PARTICIPANTS Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)-severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control). MAIN OUTCOME MEASURES Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group. RESULTS 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p

Background Patients at risk of severe exacerbations contribute disproportionally to asthma mortality, morbidity and costs. We evaluated the effectiveness and costs of using ‘asthma risk registers’ for these patients in primary care. Methods In a cluster-randomised trial, 29 primary care practices identified 911 at-risk asthma patients using British asthma guideline criteria (severe asthma plus adverse psychosocial characteristics). Intervention practices added electronic alerts to identified patients9 records to flag their at-risk status and received practice-based training about using the alerts to improve patient access and opportunistic management. Control practices continued routine care. Numbers of patients experiencing the primary outcome of a moderate-severe exacerbation (resulting in death, hospitalisation, accident and emergency attendance, out-of-hours contact, or a course/boost in oral prednisolone for asthma), other healthcare and medication usage, and costs over 1 year were derived from practice-based records. Results There was no significant effect on exacerbations (control: 46.5%; intervention: 53.6%, OR, 95% CI 1.30, 0.93 to 1.80). However, this composite outcome masked relative reductions in intervention patients experiencing hospitalisations (OR 0.50, 95% CI 0.26 to 0.94), accident and emergency (OR 0.74, 95% CI 0.42 to 1.31) and out-of-hours contacts (OR 0.79, 95% CI 0.45 to 1.37); and a relative increase in prednisolone prescription for exacerbations (OR 1.31, 95% CI 0.92 to 1.85). Furthermore, prescription of nebulised short-acting β-agonists reduced and long-acting β-agonists increased for intervention relative to control patients. The adjusted mean per patient healthcare cost was £138.21 lower (p=0.837) among intervention practices. Conclusion Using asthma risk registers in primary care did not reduce treated exacerbations, but reduced hospitalisations and increased prescriptions of recommended preventative therapies without increasing costs.

Background: Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma. Methods: After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 µg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 µg/day (n=448) or budesonide 1600 µg/day (n=441) for 12 weeks. Results: Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1–3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p

Introduction and objectives Technical errors in the use of inhalers are associated with poor asthma control. This study evaluated achievement of mastery in a training environment using a randomised cross-over design (stage 1), followed by randomization into a prospective 12-week trial to assess maintenance of mastery in patients receiving inhaled corticosteroids (ICS)/long-acting β2-agonists (LABA) via SPIROMAX versus ICS/LABA received via TURBOHALER (stage 2). Methods Patients with asthma were randomised to a 6-step training protocol using empty Spiromax and empty Turbohaler devices. The proportion of patients achieving and maintaining inhaler mastery, respectively defined as the absence of health care professional (HCP)-observed errors by training step 3 (instructional video) in stage 1, and the absence of HCP-observed errors after 12 weeks of inhaler use in stage 2, were analysed using logistic regression. The maintenance of independent expert video-observed inhaler mastery was analysed using logistic regression. Total observed errors (HCP and technology) were analysed using a negative binomial regression model. Vitalograph Pneumatic Spirometry results were compared using a Mann Whitney U test. Results A total of 493 (89.1%) patients (stage 1) and 305 (61.9%) (stage 2) were eligible for the full analysis set. The odds of maintaining inhaler mastery were not significantly different for patients using either inhaler, although achieving inhaler mastery was significantly greater in patients using Spiromax compared with Turbohaler at baseline. A higher, non-significant percentage of patients using Spiromax maintained inhaler mastery (assessed by HCPs). This result was supported by significantly higher odds of maintaining mastery when HCP errors were calibrated using independent video assessment in patients using Spiromax (consented videos available for 243/305 patients [79%]). Maintaining inhaler mastery improved asthma control in both treatment groups and was not significantly different (Table 1). Conclusions The proportion of patients achieving inhaler mastery at baseline was significantly greater for Spiromax compared with Turbohaler; no significant difference was found in inhaler mastery at 12 weeks. Patients using Spiromax made significantly fewer errors overall (HCP-observed and HCP- and technology-observed) than patients using Turbohaler. Maintaining inhaler mastery improved asthma control in both treatment groups. Independent video assessment can assist HCPs in evaluating device mastery, and is proposed as the gold standard in such studies.

Introduction Asthma and COPD have traditionally been viewed as distinct diseases. While they have overlapping biological mechanisms, past studies often focused on specific aspects of each disease based on a single diagnostic label, and many clinical trial populations were defined by strict enrolment criteria with limited generalisability. NOVELTY is a prospective, multinational, observational, longitudinal cohort study aiming to enrol 14,800 patients aged ≥12 years with a diagnosis or suspected diagnosis of asthma and/or COPD. In this population, the objectives of NOVELTY are to: (i) describe patient characteristics, treatment patterns and burden of illness over time in clinical practice; and (ii) use biomarkers and clinical parameters to identify phenotypes and endotypes associated with differential outcomes for symptom burden, clinical evolution and healthcare utilisation. Aim This feasibility analysis of electronic medical records (EMRs) aimed to understand the potential study population, assess patient numbers across disease severities and evaluate EMRs as a data source for NOVELTY. Methods EMRs from patients with asthma and/or COPD were identified from national databases covering primary and specialist care in 11 countries (Table). Disease severity was classified using treatment- and/or lung function-based algorithms for asthma and COPD. EMR variable coverage and completeness were assessed for standardised clinical, laboratory and physiological data and patient-reported outcomes (PROs). Results EMRs for 921,888 patients with asthma, 958,945 with COPD and 117,893 with both diagnoses were identified. EMRs routinely documented patient demographics and characteristics, but many disease- and treatment-related data, and PROs/symptoms required for evaluation of disease severity and clinical outcomes were frequently missing (not collected or not documented; Table). Disease severity could not be classified in 561,837 patients (asthma) and 355,743 patients (COPD), representing 22−100% and 7−85% of patients across countries. Conclusions EMR analysis revealed numbers of patients per country potentially eligible for NOVELTY. Many variables required to meet NOVELTY objectives were missing in EMRs (e.g. lung function and PRO/symptoms); therefore, variables in NOVELTY will primarily be documented in electronic case report forms, not EMRs. The lack of lung function data in many countries suggested divergences in diagnosis of asthma/COPD between clinical guidelines (which include lung function tests) and clinical practice.

Background We evaluated the effect of once-daily tiotropium Respimat® 5 µg on lung function, asthma exacerbation and asthma symptom control among patients with symptomatic asthma receiving inhaled corticosteroids (ICS; ≥800 μg/day budesonide or equivalent) + long-acting β2-agonist (LABA). Methods Data were pooled from two replicate, double-blind, placebo-controlled, 48-week, parallel-group studies of once-daily tiotropium 5 µg versus placebo, both delivered via the Respimat® SoftMist™ inhaler (PrimoTinA-asthma®: [NCT00772538][1], [NCT00776984][2]). Eligible patients had: ≥5-year history of asthma diagnosed before the age of 40 years; seven-question Asthma Control Questionnaire (ACQ-7) score of ≥1.5; experienced ≥1 exacerbation during the previous year. Patients were either lifelong non-smokers, or ex-smokers (

Background In 2014, the Royal College of Physicians published the National Review of Asthma Deaths. This confidential enquiry into 195 confirmed asthma deaths in the UK highlighted that two thirds of these deaths were associated with potentially modifiable prescription factors including excessive short-acting beta agonist (SABA) use without review and prescription of long acting beta agonists (LABA) without inhaled corticosteroids (ICS), the latter of which have been associated with higher mortality. 1 Aim The aim of this project was to determine how widespread these two modifiable prescription factors are in the treatment of asthma in UK general practice. Methods Primary Care data were obtained from the Optimum Patient Care Research Database (OPCRD). Extraction criteria included patients with a current diagnosis of asthma, at least two years of continuous medical records and at least one asthma prescription in the preceding 12 months. Those who: had a comorbid diagnosis of COPD, had received no treatment for the past 12 months and children Results 94,955 asthma patients met the inclusion criteria, of which 12661 (13%) were children. LABAs with no ICS had been prescribed to 402 patients (0.4%). A total of 5032 patients (5.3%) had been prescribed ≥ 12 SABA inhalers, ranging from 13–136 inhalers of which 1965 (39%) had not had an asthma review. Among these, 117 were children, 0.92% of the total. Conclusion These data, covering a large GP population, suggest evidence of non-guideline recommended prescribing which might contribute to increased risk to asthma patients. Prescribers should consider implementing system alerts to identify and review such prescribing behaviours. Reference 1 Lee C, Corren J. Budesonide/formoterol in the treatment of asthma. Expert Rev Respir Med 2008; 2 :551–64

Introduction and objectives Despite asthma being one of the most prevalent worldwide chronic diseases, there remains a wide variation in prevalence. 1 The United Kingdom’s (UK) National Review of Asthma Deaths 2 suggests avoidable factors play a part in as many as three-quarters of cases of asthma death. There is need to highlight and address many aspects of asthma care including the variation in diagnosis across all ages to enable appropriate treatment and improve symptom control. Here we investigate the relationship between prescribing respiratory medications and making the diagnosis of asthma, in UK primary care. Methods GP recorded data were collected from 72 UK general practices participating in the pilot British Lung Foundation asthma management program in 3 health authority areas, (two Clinical Commissioning Groups in England and one Health Board in Scotland). A retrospective analysis was undertaken of the Optimum Patient Care Research Database. This included data on child and adult patients (aged between 0 and 89) in receipt of asthma medication without a diagnosis of a chronic respiratory disease, classified by the absence of a QoF recorded asthma diagnosis. Asthma medications prescribed in the previous 12 months were identified (beta2-agonists, inhaled corticosteroids, cromones or montelukast). Results 39,124 patients received at least one respiratory medication in the 12 months prior to data collection. Of these, 9,761 (25.0%) had no clinical diagnosis ever recorded for asthma or COPD. 3,655 patients were prescribed 2 or more respiratory prescriptions without a coded respiratory disease and 982 patients had a lower respiratory tract infection recorded within the same period. Conclusion These results raise concern about over and under-treatment of children and adults in whom no diagnosis of asthma or any other chronic respiratory disease has been made. It is important that future Primary Care studies highlight the importance of early accurate diagnosis before starting treatment. Also, we suggest the present UK national prevalence and morbidity data are likely to underestimate the total burden of asthma within the Primary Care setting. References 1 The NHS Atlas of Variation in Healthcare for Respiratory Disease, 2012 2 The National Review of Asthma Deaths London, NRAD, 2014

Introduction Patients with severe asthma are estimated to comprise 5–10% of the total asthma population but contribute disproportionately to the overall burden of disease. A growing body of evidence exists that implicates steroid exposure in morbidity and healthcare costs among this group. Aim This study sought to quantify the additional healthcare costs associated with steroid exposure among patients with severe asthma. Methods Data on patients severe asthma (GINA treatment step 5 with ≥4 prescriptions/year oral corticosteroids, n = 808), was obtained from the Optimum Patient Care Research Database (OPCRD) database along with age and gender matched mild/moderate asthma patients (GINA treatment step 2/3, n = 3975) and non-asthmatic controls (rhinitis only, n = 1865) Data included details of all scheduled and unscheduled healthcare consultations and details of prescribed medicines. Data on service use were extracted for the two most recent years for which observations were available. Healthcare contacts were monetised using unit costs extracted from the Personal Social Services Research Unit’s reference costs and for drugs using Prescription Cost Analysis data. All costs were expressed in their 2013 equivalents. Sensitivity analyses related to identification of staff providing specific consultations or activity, and high/low estimates based on assumptions used were produced. Mean high/low healthcare costs over two years by group were estimated and compared as were costs estimated separately for healthcare contacts and prescribed medicines. Results As shown in Table 1 mean per patient drug, healthcare activity and combined drug and activity costs were significantly higher for the severe asthma group relative to the mild/moderate group with asthma and the non-asthma controls in both high and low cost scenarios. The mean difference in combined cost between the severe and non-asthma controls groups was between £5,031 (low cost) and £5,545 (high cost) depending on the cost scenario and £4,098 (low cost) and £4,510 (high cost) compared to the mild asthma group. Conclusions Patients with severe asthma matched by age and gender have significantly greater direct healthcare costs compared to patients with mild/moderate asthma and non-asthmatic subjects.

Introduction and objectives Fluticasone propionate/salmeterol (FP/SAL), can be delivered by metered-dose inhaler (MDI) or dry powder inhaler (DPI). The choice of device may affect adherence to and effectiveness of treatment. Although only 1000 mcg/day DPI is licensed for the treatment of COPD in the UK, the MDI and lower doses are regularly used in real-world practice. The aim of this study was to compare the effectiveness and safety of FP/SAL MDI or DPI at two doses (500 and 1000 mcg/day) in COPD patients. Methods Historical, matched cohort study using the Optimum Patient Care Research Database in patients with COPD, aged ≥35 years and initiating with FP/SAL via either MDI or DPI. Conditional Poisson regression and conditional logistic regression were used respectively to compare the rate of moderate/severe COPD exacerbations and the odds of diagnosis of pneumonia and diabetes mellitus (including anti-diabetic drug prescriptions) between MDI and DPI during one year outcome period. Models were adjusted for the respective baseline values of the outcome variable of interest where possible. Addition of LAMA therapy during the outcome period was compared using conditional logistic regression. Results 472 and 1172 patients initiated on FP/SAL at 500 mcg/day and 1000 mcg/day, respectively. The rate of moderate/severe COPD exacerbations was significantly lower for patients prescribed MDI versus DPI initiating with 500 mcg/day of FP/SAL; no significant difference was observed between MDI and DPI for those initiating at 1000 mcg/day. There were no significant differences in the odds of diagnosis of diabetes mellitus or pneumonia between MDI and DPI, irrespective of the initiation dose of FP/SAL (Table 1). LAMA prescription during the outcome period was significantly lower for patients prescribed MDI versus DPI initiating at 1000 mcg/day; no significant difference was observed between MDI and DPI for those initiating at 500 mcg/day. Conclusions This study showed greater reduction in exacerbations for patients using MDI than those using DPI when initiating with FP/SAL 500 mcg/day; no differences in exacerbation reduction and safety were seen for FP/SAL at 1000 mcg/day. Fewer patients using MDIs than DPIs at 1000 mcg/day were prescribed LAMAs, suggesting less need for treatment intensification.

Following the 1994 Lancet paper showing benefits of long-acting β-agonists (LABAs) in adults with asthma,1 British Paediatric Respiratory Society surveys have consistently recommended undertaking similar studies appropriately designed for children. Adult outcome measures should not be extrapolated into childhood, which explains why early studies indicated LABAs may be less helpful in children.2 With the advent of the Medicines for Children Research Network (MCRN) in 2004, the Health Technology Assessment (HTA) put out a call for children's medicines studies in 2005. The Management of Asthma in School Children On Therapy (MASCOT) study was funded in January 2006 pending Pharma approval to supply the medicines (fluticasone, fluticasone–salmeterol combination treatment and montelukast) as National Institute for Health Research funding does not include excess treatment costs. This task took 12 months including lengthy discussions with Merck, Sharp and Dome (MSD) about methodology and statistics. The protocol required 900 children to use inhaled corticosteroids (ICS) for a 4 week open run-in followed by 48 weeks (double blind, double dummy) taking ICS, ICS plus LABA or ICS plus montelukast. The primary outcome measure was the exacerbation rate. The HTA funded MASCOT research costs. MSD and GlaxoSmithKline (GSK) agreed to supply medication. There was a delay in appointing a trial coordinator to oversee the 13 sites which had readily agreed to participate. The lengthy task of writing the protocol to EU standards (in addition to the original protocol designed for HTA application) was new and baffling to many of us, as was the preparation and submission of the Clinical Trials Authorisation.

Introduction In patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by monotherapy, current treatment strategies recommend the addition of a second bronchodilator with a different mechanism of action. Once-daily QVA149 is a dual bronchodilator combining the long-acting β 2 -agonist indacaterol (IND) and long-acting muscarinic antagonist glycopyrronium (GLY). The IGNITE program comprises a series of randomised controlled trials that investigate the efficacy and safety of QVA149 in patients with moderate-to-severe COPD. Methods This overview includes data from 4 multicentre, double-bind, randomised controlled trials evaluating the effect of QVA149 110/50 μg versus IND 150 μg, GLY 50 μg, tiotropium (TIO) 18 μg (open-label in the SHINE and SPARK studies; blinded in the BLAZE study), salmeterol/fluticasone (SFC) 50/500 μg, and placebo (PBO) in patients with moderate-to-very severe COPD. Outcomes reported here are lung function, transitional dyspnoea index (TDI), health status (via the St George’s Respiratory Questionnaire [SGRQ]), and exacerbations over 6 weeks (BLAZE), 26 weeks (SHINE, ILLUMINATE), and 64 weeks (SPARK). Results Data from 5138 patients were included in this overview. QVA149 provided statistically significant and clinically meaningful bronchodilation (p Conclusion The results from the IGNITE trials demonstrate that superior improvements in lung function with once-daily QVA149 translate into meaningful therapeutic outcomes for patients with COPD as demonstrated by improved lung function, dyspnoea, health status, and reduced exacerbations.

BACKGROUND: The effect of breathing modification techniques on asthma symptoms and objective disease control is uncertain. METHODS: A prospective, parallel group, single-blind, randomised controlled trial comparing breathing training with asthma education (to control for non-specific effects of clinician attention) was performed. Subjects with asthma with impaired health status managed in primary care were randomised to receive three sessions of either physiotherapist-supervised breathing training (n = 94) or asthma nurse-delivered asthma education (n = 89). The main outcome was Asthma Quality of Life Questionnaire (AQLQ) score, with secondary outcomes including spirometry, bronchial hyper-responsiveness, exhaled nitric oxide, induced sputum eosinophil count and Asthma Control Questionnaire (ACQ), Hospital Anxiety and Depression (HAD) and hyperventilation (Nijmegen) questionnaire scores. RESULTS: One month after the intervention there were similar improvements in AQLQ scores from baseline in both groups but at 6 months there was a significant between-group difference favouring breathing training (0.38 units, 95% CI 0.08 to 0.68). At the 6-month assessment there were significant between-group differences favouring breathing training in HAD anxiety (1.1, 95% CI 0.2 to 1.9), HAD depression (0.8, 95% CI 0.1 to 1.4) and Nijmegen (3.2, 95% CI 1.0 to 5.4) scores, with trends to improved ACQ (0.2, 95% CI 0.0 to 0.4). No significant between-group differences were seen at 1 month. Breathing training was not associated with significant changes in airways physiology, inflammation or hyper-responsiveness. CONCLUSION: Breathing training resulted in improvements in asthma-specific health status and other patient-centred measures but not in asthma pathophysiology. Such exercises may help patients whose quality of life is impaired by asthma, but they are unlikely to reduce the need for anti-inflammatory medication.

Background Recent clinical trials have indicated that the long-acting antimuscarinic agent tiotropium, a once-daily long-acting bronchodilator, may provide benefit to patients with symptomatic asthma. We investigated primary efficacy data (lung function, risk of severe exacerbation and seven-question Asthma Control Questionnaire [ACQ-7] response) from five Phase III, randomised, double-blind, parallel-group trials that evaluated the efficacy and safety of once-daily tiotropium add-on versus placebo add-on (all tiotropium doses delivered via the Respimat ® SoftMist™ inhaler) in adults with symptomatic asthma on inhaled corticosteroid (ICS) ± long-acting β 2 -agonist (LABA) maintenance therapy. Methods Two 48-week trials of tiotropium Respimat ® 5 µg (PrimoTinA-asthma ® : NCT00776984, NCT00772538) in patients on high-dose ICS (≥800 µg budesonide or equivalent) + LABA; two 24-week trials of tiotropium Respimat ® 5 µg and 2.5 µg (MezzoTinA-asthma ® : NCT01172808, NCT01172821) in patients on moderate-dose ICS (400–800 µg budesonide or equivalent); one 12-week trial of tiotropium Respimat ® 5 µg and 2.5 µg (GraziaTinA-asthma ® : NCT01316380) in patients on low-dose ICS (200–400 µg budesonide or equivalent). Results 3476 patients were treated, of whom 1128 received tiotropium Respimat ® 5 µg. Once-daily tiotropium Respimat ® 5 µg significantly improved lung function (Table) in patients with not fully controlled asthma receiving low- to high-dose ICS. In addition, tiotropium Respimat ® 5 µg reduced the risk of severe exacerbations versus placebo (co-primary end point) in patients on high-dose ICS + LABA (hazard ratio 0.79; p = 0.0343), and there was an increase in ACQ-7 responder rate (co-primary end point) with the5 µg dose (odds ratio 1.32; p = 0.0308) compared with placebo in patients on moderate-dose ICS. Conclusion Once-daily tiotropium Respimat ® significantly improves lung function in adult patients with symptomatic asthma receiving a range of doses of ICS, including even high-dose ICS + LABA, suggesting a potential role for this treatment as add-on to ICS in adults with symptomatic asthma.

The updated National Institute for Health and Clinical Excellence (NICE) chronic obstructive pulmonary disease (COPD) guidelines1 and the draft national strategy for COPD2 have recommended a change in the classification of airflow obstruction severity to align them with international classifications. NICE's 2004 guidelines recognised that disease severity is not the same as the severity of airflow obstruction and has recommended using other measures such as the Medical Research Council (MRC) dyspnoea scale, exacerbation frequency and multicomponent indices.3 However, UK …

Introduction and Objectives Little is known about the 24-hour profile of COPD symptoms. This study assessed the frequency/severity of 24-hour symptoms and their impact on patients’ well-being. Methods This cross-sectional, observational study was conducted in patients with stable COPD. Baseline night-time, early-morning and day-time symptoms (symptom questionnaire), dyspnoea (modified Medical Research Council dyspnoea scale [mMRC]), health status (COPD Assessment Test [CAT]), anxiety/depression levels (Hospital Anxiety and Depression Scale [HADS]) and sleep quality (COPD and Asthma Sleep Impact Scale [CASIS]) were assessed. Primary endpoint: baseline frequency, severity and inter-relationship of night-time, early-morning and day-time symptoms; secondary endpoints: relationship between 24-hour symptoms and dyspnoea, health status, anxiety/depression and sleep quality. Results 727 patients were recruited from eight countries: 65.8% male, mean ± SD age 67.2 ± 8.8 years, mean ± SD% predicted FEV 1 52.7 ± 20.6%. Early-morning/day-time symptoms were most frequent; however night-time symptoms were common (Table). Symptom severity was comparable during the night-time, early-morning and day-time. In the week prior to baseline, 56.7% patients had symptoms throughout the 24-hours (79.9% in 2 or 3 parts of the day). Breathlessness was most common (71.4% patients); its prevalence increased throughout the 24-hours (32.1% night-time, 51.6% early-morning, 65.2% day-time). Dyspnoea, health status, anxiety/depression and sleep quality were worse in patients with night-time, early-morning or day-time symptoms versus patients without symptoms in each period (all p Conclusions Most patients had COPD symptoms throughout the 24-hours. Dyspnoea, health status, anxiety/depression levels and sleep quality were significantly worse in patients who had symptoms in any part of the day.

Background Treatment for chronic obstructive pulmonary disease (COPD) includes both bronchodilating and anti-inflammatory therapies. However majority of patients with COPD show corticosteroid resistance and alternative therapies are need. AKL1 is a patented botanical formulation containing extracts of Picrorhiza kurroa , Ginkgo biloba , and Zingiber officinale which has shown anti-inflammatory effects in vitro . Methods We undertook a randomised double-blind, placebo-controlled trial to determine the safety and efficacy of AKL1 in patients with a clinical labelled diagnosis of COPD and Leicester Cough Questionnaire (LCQ) score of Results Of 33 (19 male) patients mean (SD) age of 67 (9.4) years 57.9 (17.2) FEV1% predicted enrolled into the study, 15 (45%) patients were smokers and 16 (49%) were ex-smokers. Twenty patients were randomised to AKL1 and 13 to placebo. The mean (SD) change from baseline in LCQ score at 8 weeks was 2.3 (4.9) in the AKL1 group and 0.6 (3.7) in the placebo group (p = 0.43). The St. George’s Respiratory Questionnaire score improved significantly more in the AKL1 treatment group (mean [SD], -7.7 [11.7]) than in the placebo group ( + 1.5 [9.3]; p = 0.042). There were no significant differences between treatment groups in change from baseline to week 8 in other patient-reported measures, lung function, or the 6-minute walk distance. Five patients reported adverse events. Chest infections were diagnosed in one patient in each treatment allocation group. In the AKL1 group, one patient reported nightmares and one patient had right shoulder pain at the baseline visit; and one patient had influenza at the final visit. Conclusion Further study is needed with a larger patient population and over a longer duration to better assess the effects of add-on therapy with AKL1 in COPD

Objectives According to NHS QOF (Quality and Outcomes Framework) figures, 3.3 million UK citizens have asthma. Previous studies have shown an association of asthma with increased direct and indirect healthcare costs, but similar studies have not been conducted specifically for UK asthma patients. The aim of the current study is to assess the impact of poor asthma control on UK patients treated with ICS + LABA maintenance treatment. Methods Data were from the 2010 and 2011 UK National Health and Wellness Survey (NHWS), an Internet-based questionnaire from a representative sample of UK adults stratified by age and gender. 701 respondents self-reported a diagnosis of asthma without concomitant COPD, chronic bronchitis, or emphysema and were currently being treated with ICS + LABA. Patients Not Well Controlled (NWC) according to ACT (score Results A greater proportion of the 452 NWC patients (64% of the overall sample) go to emergency (21% vs. 14%, p = 0.016) or are hospitalised (13% vs. 8%, p = 0.022), in comparison with the WC; Their mental and physical HR-QoL is lower (SF-12 MCS: 43 vs. 47/100; PCS: 40 vs. 48/100; Health utility: 0.65 vs. 0.74/1.00; all p’s Conclusions Over 60% UK ICS + LABA-treated adult patients are poorly controlled. Poor control is associated with lower HR-QoL, greater healthcare use and productivity impairment, but not with significantly different levels of adherence to WC patients. The recognition of patients remaining symptomatic and utilising healthcare resource whilst treated with ICS + LABA maintenance therapy is an important step to improving their management.

Introduction and Objectives Previous studies have shown that overall asthma care can vary greatly between practises. In this study we evaluate the recorded asthma prevalence and characterize asthma control and risk profiles of real-life asthma patients from 210 practises managed within UK primary care. Methods Electronic practise data was extracted from patients with asthma from 210 practises across the UK Patients included in the analysis were ≥18 years, had clinician-diagnosed asthma (defined as a diagnostic Read code compatible with the UK Quality and Outcomes Framework [QoF] for asthma) and were receiving current asthma therapy (≥1 asthma prescriptions within the last 2 years). Eligible patients were sent asthma management questionnaires to capture patient-reported outcomes. Pooled practise and patient data were used to characterize patients in terms of their control status (as classified by the Global INitiative for Asthma [GINA] and Royal College of Physician three questions [RCP3]) and risk status (stratified according to exacerbation frequency [Read code defined acute exacerbations and number of courses of acute oral steroids in previous 12 months], with high risk defined as ≥2 exacerbations annually). Results From 210 practises across the UK there was an asthma prevalence of 5.9%, comprising 80280 adult patients and comparing to a UK QoF-assessed prevalence of 5.8%. The percentage of patients per practise with uncontrolled asthma (Median [IQR]) was 18.8% (9.1, 26.7) while the percentage per practise with no recorded RCP3 data was 18.9 (12.4, 45.9). 3.2% (n=2594) of the patients were classified as being high risk. Conclusions A high proportion of patients managed in routine UK primary care have sub-optimal asthma control. More patients at BTS management stages 4 and 5 have uncontrolled asthma and suffer from a greater number of exacerbations. RCP3 recording varies between practises, and can be poorly recorded.

Introduction and Objectives Asthma therapy reviews aim to minimise side-effects and achieve cost-effective asthma control. We set out to examine the impact of switching from a fixed dose combination therapy inhaled corticosteroid/long-acting β2 agonist (FDC ICS/LABA) therapy via dry power inhaler (DPI) or metered-dose inhaler (MDI) to beclometasone dipropionate/formoterol (BDP/FOR) via MDI at the same or reduced dose of ICS in stable patients. Methods We utilised the UK’s Optimum Patient Care Research Database to identify suitable primary care patients (aged 18–80 years) with asthma (diagnostic code and/or ≥2 asthma prescriptions in the last year) who were changed from FDC ICS/LABA to a prescription of BDP/FOR MDI at the same or lower BDP-equivalent ICS daily dose following a review of their existing ICS/LABA therapy. The number of exacerbations was measured as an outcome, with exacerbations defined as asthma related hospital, accident and emergency or out-of-hours attendance, GP consultations for lower respiratory tract infection and/or use of acute oral steroids (where asthma related includes all events with a lower respiratory Read code). All patients had 2 years of data: 1 year before and 1 year post therapy switch. Results Out of a total of 365 patients, 334 had complete data for the analysis. 80 of these received a lower dose of BDP/FOR while 254 received an equivalent dose. In the year immediately before their therapy review, 69.5% (n=232) of patients had no exacerbations, compared to 76.9% (n=257) of patients following the review (p=0.075 Wilcoxon signed ranks). Prior to review, 20.4% of patients had 1 exacerbation compared with 12.0% of patients after the change, while 10.2% of patients had >1 exacerbation compared with 11.1% of patients following the review. Conclusion These data suggest an increase in the number of patients not suffering from exacerbations and no deterioration in the number of exacerbations following the alteration in therapy. This indicates that BDP/FOR can be a valid therapy change in real-world patients on existing FDC ICS/LABA therapy.

Introduction and Objectives Combination therapy with an inhaled corticosteroid (ICS) and a long-acting s 2 -agonist (LABA) is the most effective treatment option for patients with asthma uncontrolled with ICS monotherapy.1 In practice, asthma symptoms remain uncontrolled or only partly controlled in many patients. A new therapy option for asthma combining the ICS fluticasone propionate (FLUT) and the LABA formoterol fumarate (FORM) in a single aerosol inhaler (FLUT/FORM; flutiform ® ), has been developed at doses of 100/10, 250/10 and 500/20 μg for twice-daily administration. In this analysis, data were pooled from up to five randomised, double-blind, parallel-group studies in order to assess the efficacy of FLUT/FORM in terms of improvement in lung function (as indicated by change in FEV 1 ). Methods The analysis included adults and adolescents with a range of asthma severities who were treated for 8 or 12 weeks with FLUT/FORM (100/10, 250/10 or 500/20 μg twice daily) or the equivalent nominal dose of FLUT monotherapy (100, 250 or 500 μg twice daily; five studies) or FORM monotherapy (10 μg twice daily; three studies). Results FLUT/FORM was associated with a significantly greater improvement in lung function, as indicated by change in FEV 1 , compared with its individual components (Abstract P110 table 1). FLUT/FORM was superior to FORM with regard to change in pre-dose FEV 1 from baseline to study end; the least-squares (LS) mean difference for FLUT/FORM vs FORM was 0.13 l (95% CI 0.07 to 0.19; p 1 from pre-dose at baseline to 2 h post-dose at study end (LS mean difference FLUT/FORM vs FLUT 0.15 L [95% CI 0.10 to 0.19; p Conclusions The combination of fluticasone/formoterol in a single aerosol inhaler is more effective than fluticasone or formoterol given alone in improving lung function for patients with a range of asthma severities.

Introduction and Objectives Poor asthma control impacts on patients9 health and reduces their quality of life. Despite a rise in the proportion of patients receiving treatment, asthma remains uncontrolled in many patients. A new therapy option combining the inhaled corticosteroid fluticasone propionate (FLUT) with the long-acting s 2 -agonist formoterol fumarate (FORM) in a single aerosol inhaler (FLUT/FORM; flutiform ® ) has been developed for the treatment of asthma. This integrated analysis of data from five randomised, double-blind, parallel-group phase 3 studies assessed the effects of FLUT/FORM compared with FLUT alone on the percentage of asthma control days. Methods Symptomatic adult and adolescent patients with mild, moderate or severe asthma were randomly assigned to receive FLUT/FORM (100/10, 250/10 or 500/20 μg twice daily) or the equivalent nominal dose of FLUT alone (100, 250 or 500 μg twice daily) for 8 or 12 weeks. Most patients randomised to treatment had uncontrolled asthma. The percentage change in asthma control days (defined as those with no use of rescue medication, an asthma symptom score reporting no symptoms and a sleep disturbance score indicating that the patient slept through the night) was assessed from baseline to study end. Results At baseline, the percentage of asthma control days was low in both groups (FLUT/FORM [n=623]: 12.8%; FLUT [n=623]: 12.6%). FLUT/FORM combination therapy was superior to FLUT alone for improvement in percentage of asthma control days. At study end, patients in the FLUT/FORM group experienced a mean of 62.4% asthma control days, an improvement of 49.6% from baseline, whereas FLUT treatment was associated with 54.8% asthma control days (42.2% change from baseline). FLUT/FORM provided a statistically significant improvement in asthma control days compared with FLUT alone (least-squares mean difference [95% CI]: 7.5% [3.21 to 11.84]; p Conclusions Fluticasone/formoterol combination therapy is superior to fluticasone monotherapy for improving the percentage of asthma control days over 8 or 12 weeks9 treatment in adults and adolescents with mild, moderate or severe asthma. These data suggest the combination of fluticasone and formoterol in a single aerosol inhaler will provide an effective option for asthma maintenance therapy.

Background It is recognised that some 45% of the population exhibit poor asthma control. Over 90% of the population possess a mobile phone (>70% over 60 years of age). Mobile technology potentially addresses the barriers of low expectations and poor concordance which are factors in poor asthma control. Hypothesis Using mobile phone recording of symptoms, lung function and medication use with instant feedback of asthma control, would improve control compared to using paper diaries. Trial design A 6-month researcher-blinded randomised controlled trial Setting UK primary care Method Using central randomisation, we allocated patients ≥12 years of age with poorly controlled asthma (ACQ>1.5) to either mobile phone or paper-based monitoring. Clinical care was provided by practice asthma nurses in accordance with SIGN/BTS guidelines. Patients were reviewed monthly until control was achieved. A researcher, blinded to allocation assessed outcomes at 3 m and 6 m. Primary outcome measure: change in Asthma Control Questionnaire score between baseline and 6 months. Results We randomised 288 patients from 32 practices (209 completed). Baseline characteristics of both groups were similar. Intention to treat analysis, before breaking the randomisation code, showed that control in both groups improved significantly and to a similar extent. ACQ: Group 1 (n=110) Baseline 2.17, 6m 1.25: Group 2 (n=99) Baseline 2.33, 6m 1.17. Mean (95% CI) improvement in ACQ: Group 1 (n=110) 0.84 (0.67, 1.02), Group 2 (n=99) 0.94 (0.77, 1.11) both p Conclusion Both groups demonstrated significant improvement in asthma control from baseline. Use of mobile phone technology provided no additional benefit over paper diaries.

Objectives To evaluate the effectiveness of using electronic registers to identify and improve management of high-risk asthma patients in primary care. Design Cluster-randomised controlled trial with stratification by high/low deprivation scores and 1-year follow-up. Participants 29 GP practices in Norfolk, UK with suitable software systems used electronic searches and clinical knowledge to identify 911 patients aged 5+ years at high risk from their asthma as defined by British asthma guidelines (severe asthma plus adverse psychosocial characteristics, including poor adherence). Intervention Intervention practices established registers of high-risk asthma patients and used an electronic alert to identify these patients at all practice encounters. This allowed reception staff to prioritise appointments and facilitate patient access to clinicians and clinical staff to review patients9 asthma at all opportunities. Practice staff received a 1-h tailored training session on the use of alerts and actions to be taken from a GP (MN) and nurse (JW). Control practices continued with routine care. Outcomes A composite measure of moderate–severe exacerbations (primary outcome, see Abstract S137 Table 1 for definition), disaggregated exacerbation-related events, consultations and medications (secondary outcomes) were derived from anonymous clinical data extracted from practice-based patient records for the year before and after implementation of registers. Results See Abstract S137 Table 1 for results of unadjusted analyses. After adjustment for relevant covariates at baseline similar effects were observed but only the effect on nebulised β-agonists prescriptions remained significant. Conclusions Use of at-risk registers had no significant effect on the overall rate of moderate–severe exacerbations. However, they were associated with increases in prescriptions of oral steroids, inhaled steroids and long-acting β-agonists, coupled with reductions in asthma hospitalisations, prescriptions of nebulised short-acting β-agonists and in failures to attend primary care appointments. Together these are suggestive of improved asthma management in the intervention group.