Background COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom’s response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace. Objective We aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR). Methods A federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners’ pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers’ secure environments, and to support federated cohort discovery queries and meta-analysis. Results A total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom. Conclusions CO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.

Background: Observational research is essential to evaluate the real-life effectiveness of asthma treatments and can now make use of outcomes derived from electronic medical records. Aim: The aim of this study was to investigate the utility of several database outcome measures in asthma. Methods: This study identified cohorts of patients with active asthma from a UK primary care database - Optimum Patient Care Research Database -approximately 10% of which was prospectively supplemented with questionnaire data. The "Questionnaire cohort" included patients aged 18-60 years with valid questionnaire data and 1 year of continuous primary care data. Separate "ICS initiation" and "ICS step-up" cohorts included patients aged 5-60 years initiated on inhaled corticosteroids (ICSs), who had 1 year of continuous primary care data before, and after, this index visit. Database measures of asthma symptom control and exacerbations were identified in the Optimum Patient Care Research Database and cross-tabulated with corresponding patient-reported (questionnaire) data. Responsiveness of the database outcomes was analyzed, using McNemar's and Wilcoxon's signed rank tests, and Poisson regression was used to estimate the association between database outcomes and future risk of database exacerbations, in the ICS initiation cohort. Results: The final study included 2,366 Questionnaire cohort patients and 51,404 ICS initiation patients. Agreement between patient-reported and database-recorded exacerbations was fair (kappa 0.35). Following the initiation of ICS, database risk domain asthma control (based on exacerbations) improved (proportion of patients with uncontrolled asthma decreased from 24.9% to 18.6%; P< 0.001) and mean number of database exacerbations decreased from 0.09 to 0.08 per patient per year (P= 0.001). However, another measure of asthma control which includes short-acting beta-agonist prescription as part of the definition did not show this improvement. Patients with prior exacerbations had a higher risk of future exacerbation (rate ratio [95% confidence interval], 3.23 [3.03-3.57]). Conclusion: Asthma control and exacerbations derived from primary care databases were responsive, with the exception of short-acting beta-agonist prescriptions, and useful for risk prediction.

Little data on UK prescribing patterns and treatment effectiveness for allergic rhinitis (AR) are available. We quantified unmet pharmacologic needs in AR by assessing AR treatment effectiveness based on the prescribing behaviour of UK general practitioners (GP) during two consecutive pollen seasons (2009 and 2010). We conducted a retrospective observational study with the data from the Optimum Patient Care Research Database. We assessed diagnoses and prescription data for patients with a recorded diagnosis of rhinitis who took rhinitis medication during the study period. We assessed the data from 25,069 patients in 2009 and 22,381 patients in 2010. Monotherapy was the initial prescription of the season for 67% of patients with seasonal AR (SAR) and 77% of patients with nonseasonal upper airways disease (NSUAD), for both years. Initial oral antihistamine (OAH) or intranasal corticosteroid (INS) monotherapy proved insufficient for >20% of SAR and >37% of NSUAD patients. Multiple therapy was the initial prescription for 33% of SAR and 23% of NSUAD in both years, rising to 45% and >50% by season end, respectively. For NSUAD, dual-therapy prescriptions doubled and triple-therapy prescriptions almost tripled during both seasons. Many patients revisited their GP regardless of initial prescription. Initial OAH or INS monotherapy provides insufficient symptom control for many AR patients. GPs often prescribe multiple therapies at the start of the season, with co-prescription becoming more common as the season progresses. However, patients prescribed multiple therapies frequently revisit their GP, presumably to adjust treatment. These data suggest the need for more effective AR treatment and management strategies.

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

Background Randomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA) such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care. Methods Medical records of adults with asthma (aged ≥18 years) prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001–2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline) and the year after (outcome) addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course) and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation). Secondary outcomes included lung function test results and short-acting β2 agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices. Results Of the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting β2 agonist during the baseline year; 67% were prescribed both. Comparing baseline and outcome years, the percentage of patients having at least one exacerbation decreased from 37% to 27% (P<0.001) and the percentage having at least one acute respiratory event decreased from 58% to 47% (P<0.001). There were no significant changes in lung function, and usage of short-acting β2 agonists (in salbutamol/albuterol equivalents) increased from a median (interquartile range) of 274 (110, 548) to 329 (110, 603) μg/day (P=0.01). Conclusion In this real-life asthma population, addition of LAMA therapy was associated with significant decreases in the incidence of exacerbations and antibiotic prescriptions for lower respiratory tract infections in the following year.

RATIONALEGuidelines advocate adding long-acting β-agonist (LABA) to inhaled corticosteroid as the preferred step-up therapy to increasing inhaled corticosteroid dose for patients with uncontrolled asthma on inhaled corticosteroid monotherapy. However, less than 5% of patients with asthma qualify for the randomized controlled trials on which guidelines are based. Thus, real-world data are needed to complement the results of randomized trials with narrow entry criteria.OBJECTIVESTo compare the effectiveness of stepping up asthma therapy with an increased dose of various types of inhaled corticosteroid as compared with add-on LABA.METHODSWe performed a historical matched cohort study using large primary care databases to compare asthma step-up therapy with small- and standard size-particle inhaled corticosteroid versus added LABA for patients 12-80 years old. As outcomes, we examined a composite of asthma control and rates of severe exacerbations.MEASUREMENTS AND MAIN RESULTSThe odds of asthma control and rates of severe exacerbations over one outcome year were comparable with increased inhaled corticosteroid dose versus added LABA. The adjusted odds ratios (95% confidence interval) for achieving asthma control with increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were 0.99 (0.88-1.12) for small-particle inhaled corticosteroid (n = 3,036 per cohort) and 0.85 (0.67-1.07) for standard size-particle inhaled corticosteroid (n = 809 per cohort). The adjusted rate ratios (95% confidence interval) for severe exacerbations, compared with inhaled corticosteroid/LABA combination inhaler, were 1.04 (0.91-1.20) and 1.18 (0.92-1.54), respectively. The results were not affected by smoking status.CONCLUSIONSWhen applied to a broad primary care population, antiinflammatory therapy using increased doses of small- or standard size-particle inhaled corticosteroid is as effective as adding LABA, as measured by outcomes important to both patients and providers. Real-world populations and outcomes need to be taken into consideration when formulating treatment recommendations.

This article was originally published online on 8 April 2015BackgroundAsthma management guidelines suggest little difference between EF and SP-ICS other than potency and therefore EF-ICS should be used at same dose as fluticasone (FP) and half the dose of SP-beclomethasone (BDP). Cohort studies suggest EF-BDP patients can achieve better asthma control than FP patients at lower doses. We compared baseline characteristics and first prescribed doses of patients initiating ciclesonide vs. SP-ICS.MethodsData from the PHARMO Database Network (pharmacy and hospital discharge records) on patients (12-60 years old) with ≥2 prescriptions for asthma therapy (2005-2012) were compared over 1 year before initiating ciclesonide vs SP-ICS. Co-morbidities were evaluated over 1 year before and after ICS initiation. To avoid inclusion of potential COPD patients, those >60 years old and those using long-acting muscarinic antagonists were excluded. Sex and age at ICS initiation; initial ICS doses (actual prescribed doses); short-acting β2-agonists (SABA) use (year before initiation); prescriptions for acute oral steroids and overall asthma control (no hospital admissions, no acute oral steroids and ≤200mcg/day salbutamol) in the year prior and including initiation date; and prescriptions of drugs for treating co-morbidities (year before and after initiation) were compared using t-test/chi-square test (p<0.05).ResultsOf 4,064 patients, 34% initiated therapy as ciclesonide and 66% as SP-ICS, with same proportion of males (36%). Differences (p<0.001, unless otherwise specified) for ciclesonide vs. SP-ICS were: mean(±SD) age (43±13 vs. 38±14 years); median(Inter Quartile Range) initial ICS doses 160(160-160) vs. 500(250-500) μg; proportion of patients not on SABA (72% vs. 57%) and on SABA daily dosage between 1-100 μg/day (21% vs. 29%), 101-200 μg/day (5% vs. 9%) and >200 μg/day (2% vs. 6%); proportion of patients not prescribed acute oral steroids (90% vs. 88%, p=0.016) and with controlled asthma (87% vs. 82%); proportion of patients prescribed nasal (44% vs. 38%) and topical (31% vs. 28%) steroid preparations, proton-pump inhibitors (41% vs. 29%) and cardiac diseases or hypertension drugs (28% vs. 21%).ConclusionsFor comparable asthma control and similar prevalence of co-morbidities, patients were prescribed triple the dose of SP-ICS versus ciclesonide. Further to this analysis, the effects on asthma control in the year following ICS initiation will be investigated. This article was originally published online on 8 April 2015 BackgroundAsthma management guidelines suggest little difference between EF and SP-ICS other than potency and therefore EF-ICS should be used at same dose as fluticasone (FP) and half the dose of SP-beclomethasone (BDP). Cohort studies suggest EF-BDP patients can achieve better asthma control than FP patients at lower doses. We compared baseline characteristics and first prescribed doses of patients initiating ciclesonide vs. SP-ICS. Asthma management guidelines suggest little difference between EF and SP-ICS other than potency and therefore EF-ICS should be used at same dose as fluticasone (FP) and half the dose of SP-beclomethasone (BDP). Cohort studies suggest EF-BDP patients can achieve better asthma control than FP patients at lower doses. We compared baseline characteristics and first prescribed doses of patients initiating ciclesonide vs. SP-ICS. MethodsData from the PHARMO Database Network (pharmacy and hospital discharge records) on patients (12-60 years old) with ≥2 prescriptions for asthma therapy (2005-2012) were compared over 1 year before initiating ciclesonide vs SP-ICS. Co-morbidities were evaluated over 1 year before and after ICS initiation. To avoid inclusion of potential COPD patients, those >60 years old and those using long-acting muscarinic antagonists were excluded. Sex and age at ICS initiation; initial ICS doses (actual prescribed doses); short-acting β2-agonists (SABA) use (year before initiation); prescriptions for acute oral steroids and overall asthma control (no hospital admissions, no acute oral steroids and ≤200mcg/day salbutamol) in the year prior and including initiation date; and prescriptions of drugs for treating co-morbidities (year before and after initiation) were compared using t-test/chi-square test (p<0.05). Data from the PHARMO Database Network (pharmacy and hospital discharge records) on patients (12-60 years old) with ≥2 prescriptions for asthma therapy (2005-2012) were compared over 1 year before initiating ciclesonide vs SP-ICS. Co-morbidities were evaluated over 1 year before and after ICS initiation. To avoid inclusion of potential COPD patients, those >60 years old and those using long-acting muscarinic antagonists were excluded. Sex and age at ICS initiation; initial ICS doses (actual prescribed doses); short-acting β2-agonists (SABA) use (year before initiation); prescriptions for acute oral steroids and overall asthma control (no hospital admissions, no acute oral steroids and ≤200mcg/day salbutamol) in the year prior and including initiation date; and prescriptions of drugs for treating co-morbidities (year before and after initiation) were compared using t-test/chi-square test (p<0.05). ResultsOf 4,064 patients, 34% initiated therapy as ciclesonide and 66% as SP-ICS, with same proportion of males (36%). Differences (p<0.001, unless otherwise specified) for ciclesonide vs. SP-ICS were: mean(±SD) age (43±13 vs. 38±14 years); median(Inter Quartile Range) initial ICS doses 160(160-160) vs. 500(250-500) μg; proportion of patients not on SABA (72% vs. 57%) and on SABA daily dosage between 1-100 μg/day (21% vs. 29%), 101-200 μg/day (5% vs. 9%) and >200 μg/day (2% vs. 6%); proportion of patients not prescribed acute oral steroids (90% vs. 88%, p=0.016) and with controlled asthma (87% vs. 82%); proportion of patients prescribed nasal (44% vs. 38%) and topical (31% vs. 28%) steroid preparations, proton-pump inhibitors (41% vs. 29%) and cardiac diseases or hypertension drugs (28% vs. 21%). Of 4,064 patients, 34% initiated therapy as ciclesonide and 66% as SP-ICS, with same proportion of males (36%). Differences (p<0.001, unless otherwise specified) for ciclesonide vs. SP-ICS were: mean(±SD) age (43±13 vs. 38±14 years); median(Inter Quartile Range) initial ICS doses 160(160-160) vs. 500(250-500) μg; proportion of patients not on SABA (72% vs. 57%) and on SABA daily dosage between 1-100 μg/day (21% vs. 29%), 101-200 μg/day (5% vs. 9%) and >200 μg/day (2% vs. 6%); proportion of patients not prescribed acute oral steroids (90% vs. 88%, p=0.016) and with controlled asthma (87% vs. 82%); proportion of patients prescribed nasal (44% vs. 38%) and topical (31% vs. 28%) steroid preparations, proton-pump inhibitors (41% vs. 29%) and cardiac diseases or hypertension drugs (28% vs. 21%). ConclusionsFor comparable asthma control and similar prevalence of co-morbidities, patients were prescribed triple the dose of SP-ICS versus ciclesonide. Further to this analysis, the effects on asthma control in the year following ICS initiation will be investigated. For comparable asthma control and similar prevalence of co-morbidities, patients were prescribed triple the dose of SP-ICS versus ciclesonide. Further to this analysis, the effects on asthma control in the year following ICS initiation will be investigated.

BACKGROUND: Because randomized controlled trials of established pediatric asthma therapies are expensive and difficult to perform, observational studies may fill gaps in the evidence base.OBJECTIVES: To compare the effectiveness of representative small-particle inhaled corticosteroid (ICS) with that of standard size-particle ICS for children initiating or stepping up ICS therapy for asthma (analysis 1) and to compare the effectiveness of ICS dose step-up using small-particle ICS with adding long-acting beta(2)-agonist (LABA) to the ICS (analysis 2).METHODS: These historical matched cohort analyses drew on electronic medical records of children with asthma aged 5 to 11 years. Variables measured during 2 consecutive years (1 baseline year for confounder definition and 1 outcome year) included risk-domain asthma control (no hospital attendance for asthma, acute oral corticosteroids, or lower respiratory tract infection requiring antibiotics) and rate of severe exacerbations (asthma-related emergency, hospitalization, or oral corticosteroids).RESULTS: In the initiation population (n = 797 in each cohort), children prescribed small-particle ICS versus standard sizeeparticle ICS experienced greater odds of asthma control (adjusted odds ratio, 1.49; 95% CI, 1.10-2.02) and lower severe exacerbation rate (adjusted rate ratio, 0.56; 95% CI, 0.35-0.88). Step-up outcomes (n = 206 in each cohort) were also significantly better for small-particle ICS, with asthma control adjusted odds ratio of 2.22 (95% CI, 1.23-4.03) and exacerbations adjusted rate ratio of 0.49 (95% CI, 0.27-0.89). The number needed to treat with small-particle ICS to achieve 1 additional child with asthma control was 17 (95% CI, 9-107) for the initiation population and 5 (95% CI, 3-78) for the step-up population. Outcomes were not significantly different for stepped-up small-particle ICS dose versus ICS/LABA combination (n = 185 in each cohort).CONCLUSIONS: Initiating or stepping up the ICS dose with small-particle ICS rather than with standard sizeeparticle ICS is more effective and shows similar effectiveness to add-on LABA in childhood asthma. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

Allergic rhinitis (AR) is poorly controlled. Treated patients, even those on multiple therapies still experience symptoms. In a UK survey, 70.5% of moderate-to-severe AR patients took ≥2 medications (either Rx or over the counter) in an attempt to achieve better and faster symptom relief. To explore the extent of co-prescribing by UK general practitioners (GPs) during the hay-fever season in patients with seasonal AR (SAR), perennial AR (PAR), and comorbid asthma. A retrospective database study using the Optimum Patient Care Research Database consisting of data extracted from GP records supplemented with patient-reported outcomes from questionnaires. Patients included in the analysis had a recorded AR diagnosis and ≥1 AR therapy scripts during 1st March 2010 to 31st Augu37st 2010. In all, 22,381 AR patients were included. Results are summarized in the table. Combination therapy Start of season End of season 1536 (24.6) 2296 (41.6) 780 (23.9) 1805 (55.2) 3885 (36.4) 5041 (47.2) 650 (22.2) 1415 (48.4) In contrast to previous surveys, these data relate to prescriptions only and show a high level of co-prescribing behavior among UK GPs. There was a significant shift to combination therapy during the season, particularly for PAR patients, with strong co-prescription evident regardless of asthma co-morbidity. These data indicate that (i) UK GPs are aware that current therapy provides insufficient symptom relief, (ii) that AR is a costly disease to treat requiring several GP visits over the season for therapy modification and (iii) there is a need for an AR therapy which provides more complete symptom relief.

Aim: Patient-reported exacerbations (PRE) can be hard to capture. We assessed whether a database exacerbation measure (DBE) reliably reflected the patient experience. Methods: We used a UK research database to select clinical and asthma questionnaire records of patients aged 18–60yrs with an asthma diagnosis, no other chronic respiratory diseases and not receiving maintenance oral steroids. DBEs were identified in the clinical records as: a course of oral steroids with evidence of respiratory review (OS) and/or asthma-related hospital admission or emergency room (ER) attendance. PREs over the same period were identified as a positive questionnaire response to any of the 3 questions: In the last 12 months, have you (i)Received courses of OS for worsening asthma? (ii)Been admitted to hospital due to asthma? (iii)Attended ER for asthma? The strength of association between the endpoints was assessed using Kendall's Tau-b (τb). Results: Of a total of 1666 patients (62% female, 24% current smokers), 25% reported ≥1 PRE, and 10% had ≥1 DBE. Some co-linearity was found between PRE items (i)&(ii). A moderate association was found between DBE and PRE (τb=0.419; p<0.001), the table shows the relationship between the measures. View this table: Association between PREs & DBEs Conclusion: All outcome measures have their limitations. Despite the different sources of measurement error for DBE and PRE definitions (eg. known under-reporting of hospitalisations in UK primary care records), these measures were found to have a moderate positive association.

Background : Correct inhalation technique is crucial for asthma therapy delivery. Incorrect technique could influence patient outcomes. Aim :To investigate inhaler technique with patient characteristics and outcomes in real-life primary care setting. Methods :Retrospective,cross sectional study using international iHARP database including electronic patient records and questionnaires from 8 countries. Asthma patients (GINA step 3-4) performing no errors were compared with those performing ≥1 error using Mann-Whitney test for numerical and Χ 2 test for categorical variables. Errors were defined by iHARP steering committee and recorded by qualified nurses from 2011-2013. Results : Of 3681 patients, 623 (17%) used Diskus (67% female; median age 52 [IQR:41-63]). 55% of those performed ≥1 error. Female and obese patients performed more errors (p=0.024,p=0.036 respectively). 26% of patients with ≥1 error had uncontrolled GINA-defined asthma vs. 17% of patients having no errors (p=0.017). Similar association observed for ATAQ score (p=0.003). 19% in the ≥ 1 error and 10% in the no error group had ≥ 1 annual in-patient admission/A&E attendance(p=0.001). Error and exacerbation risk association is shown below. Conclusion : Asthma patient inhaler technique remains poor and is associated with poor asthma control,and higher hospitalisation and exacerbation risk. Obese and female patients are most at risk.

Purpose: To investigate the clinical and cost effectiveness of switching real-life asthma patients from other types of inhalers to the Easyhaler((R)) (EH) for the administration of inhaled corticosteroids (ICS).Patients and methods: Historical, matched-cohort study of 1,958 asthma patients(children and adults) treated in UK primary-care practices, using data obtained from the Optimum Patient Care Research Database and Clinical Practice Research Datalink. Other inhalers (OH) included pressurized metered-dose inhalers, breath-actuated inhalers, and dry-powder inhalers, delivering beclomethasone, budesonide, fluticasone, or ciclesonide. Patients remaining on OH unchanged (same drug, dosage, and device; n=979) were matched 1:1 with those switched to the EH (beclomethasone or budesonide) at the same or lower ICS dosage (n=979), based on age, sex, year of index patient review/switch, most recent ICS drug, dosage, and device, and the number of severe exacerbations and average daily short-acting beta(2) agonist (SABA) dosage in the preceding year. Clinical outcomes and health care costs were compared between groups for 12 months before and after the switch. Co-primary clinical outcomes were: 1) risk domain asthma control (RDAC) - no asthma-related hospitalization, acute oral steroid use, or lower respiratory tract infection (LRTI); 2) exacerbation rate (American Thoracic Society [ATS] definition) - where exacerbation is asthma-related hospitalization or acute oral steroid use; 3) exacerbation rate (clinical definition) - where exacerbation is ATS exacerbation or LRTI; and 4) overall asthma control (OAC) - RDAC plus average salbutamol-equivalent SABA dosage <= 200 mu g/day. Non-inferiority (at least equivalence) of EH was tested against OH for the four co-primary outcomes in order (hierarchical approach) by comparing the difference in proportions of patients [EH-OH] achieving asthma control or having no exacerbations in the outcome year, using a limit of 10% difference. Results: Non-inferiority was shown for the EH for all four co-primary outcomes. There were no significant differences between groups for RDAC or exacerbation rates, but EH patients were - significantly more likely to achieve OAC (adjusted odds ratio [95% confidence interval]:1.26 [1.05, 1.52]), as significantly more EH than OH patients had an average SABA dosage of <= 200 mu g/day (52% versus 47%, respectively; P<0.001). Mean asthma-related health care costs increased from baseline to outcome years in both groups, but SABA costs increased significantly more in OH than EH patients (mean difference (sic)5.5/patient/year) and consultation costs decreased significantly more in EH than OH patients (mean difference (SIC)13.5/patient/year).Conclusion: Typical asthma patients may be switched from other ICS devices to the Easyhaler((R)) with no reduction in clinical effectiveness or increase in cost.

Aim: Improved understanding of patient characteristics associated with exacerbations (EXBs) may provide opportunity to minimize future risk. We assessed whether database asthma control can predict future EXBs. Methods: Used a research database to select clinical records of patients aged 18–60yrs with an asthma diagnosis, continuous records over 1 baseline & 1 outcome yr and no other chronic respiratory disease or maintenance oral steroids. Two baseline control measures were evaluated: risk domain asthma control (RDAC) & overall control (OAC). RDAC was absence of: exacerbations, unplanned asthma-related out patient appointments, and antibiotics with evidence of respiratory review (ABX). OAC was: RDAC+average salbutamol ≤200µg/day. RDAC/OAC components predictive of outcome EXBs in univariable models were entered into a multivariable model and stepwise reduced. EXBs were: oral steroid courses with evidence of respiratory review (OS), asthma-related hospital admission or emergency room [ER] attendance. Results: Of 1558 patients (60% female), 73% and 42% satisfied criteria for RDAC and OAC control, respectively, at baseline. Baseline Predictors of EXB risk Rate Ratio(95%CI) p-value Univariable analysis RDAC (uncontrolled)∗ 2.78(2.04–3.70) <0.001 OAC (uncontrolled)∗ 1.69(1.23–2.33) <0.001 OS 0 1.00 1 2.33(1.58–3.42) <0.001 ≤2 2.53(1.54–4.17) ER attendance 0 1.00 1 1.58(1.06–2.34) <0.001 ≤2 2.43(1.59–3.71) ER attendance 0 1.00 0.037 ≤1 2.21(1.05–4.66) ∗Controlled RR=1.00 Conclusions: Classification as RDAC or OAC at baseline predicted lower EXB rates in the following year. OS, ABX and asthma-related ER attendance independently predicted increased EXB risk regardless of “current control” as indicated by salbutamol use.

Real-life studies are needed to determine the cost-effectiveness of asthma therapies in clinical practice. To compare the cost-effectiveness of extrafine-particle inhaled corticosteroid (ICS) with standard size-particle ICS in the United Kingdom (UK) and United States (US). These retrospective matched cohort analyses used large electronic databases to study asthma-related outcomes for patients in the UK (12–60 years old; n=1730) and US (12–80 years; n=10,312) prescribed extrafine beclomethasone or fluticasone as their first ICS therapy for asthma. Patients were matched on demographic characteristics and asthma severity during 1 baseline year, and asthma control and asthma-related costs were compared during 1 outcome year. In both the UK and US, adjusted odds of risk-domain asthma control were similar, whereas the odds of overall control (no hospitalisation or oral steroids for asthma, no antibiotics for lower respiratory infection, limited reliever use) were greater for extrafine ICS in both countries (UK odds ratio, 1.23; 95% confidence interval (CI), 1.01–1.50). Asthma-related annual costs, adjusted for baseline, were significantly lower for extrafine-particle ICS cohorts in both countries (UK difference, −£66 (95% CI,−93 to −37)). Cost-effectiveness analyses using the two measures of asthma control found 92 and 98% probabilities of extrafine-particle ICS being the preferred treatment strategy (less costly and more effective than standard size-particle ICS) in the UK, and 84 and 100% probabilities in the US. Initiating ICS therapy for asthma as extrafine-particle ICS seems the dominant treatment option (less costly and more effective) compared with standard size-particle ICS in both the UK and the US. A retrospective matched cohort study shows that extrafine inhaled corticosteroid therapy is a cost-effective option for treating asthma. Current treatment guidelines recommend the use of inhaled corticosteroids as a first-line therapy for patients with asthma but such therapy can be expensive. An international team led by David Price at the University of Aberdeen in the UK compared the cost and effectiveness of extrafine inhaled corticosteroids with those of standard inhaled cortiosteroids using data from two large, well-established cohort, one from the UK and the other from the USA. They showed that patients in both countries who used extrafine inhaled corticosteroids achieved better overall control of their asthma. The annual costs of standard inhaled corticosteroids were significantly higher in both countries, suggesting the use of extrafine inhaled corticosteroids is probably the preferred treatment option.

Aim: Short-acting beta-agonist (SABA) use is an important aspect of asthma management. As patient reports can be hard to elicit, medical records are sometimes used to infer SABA use. We assessed whether database (DB) evaluation of SABA use reliably reflects patient reported (PR) use. Methods: We used a UK research database to select clinical records of patients aged 18–60yrs with an asthma diagnosis, no other chronic respiratory diseases and not receiving maintenance oral steroids. DB SABA prescribing over one year was calculated from prescription records. PR SABA use was computed from asthma questionnaire responses from the same year (assessing PR reliever use in the last week) with one "use" assumed to be 2 puffs (=200µg salbutamol) and extrapolating over 1yr. DB and PR SABA use were cross tabulated and strength of association assessed using Kendall's Tau-b (τ b ) test. Results: Among the 2425 patients (60% female, 25% current smokers), PR SABA use was consistently lower than the number of inhalers actually prescribed resulting in a weak/significant association between DB and PR SABA use (τ b =0.21; p<0.001). Association between DB & PR SABA use PR SABA uses in previous week scaled to I/Y DB SABA prescribed (I/Y) 0(%) 1(%) 2(%) 3(%) 4(%) ≥5(%) 0(%) 0 20 15 13 15 14 1(%) 44 19 15 13 8 9 2(%) 29 22 18 11 14 8 3(%) 9 8 11 12 7 7 4(%) 8 9 12 15 15 9 ≥5(%) 11 22 29 38 43 53 I/Y=inhalers per year Conclusions: The discrepancy between PR and DB SABA use may reflect under-reporting by patients, prescribing of “spares”, and/or asthma is a variable condition poorly characterised by data from a single week. The difference should be acknowledged in DB studies reporting SABA use.

Purpose: Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2-4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD.Patients and methods: Smokers and ex-smokers with COPD >= 40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease severity during 1 baseline year. During 2 subsequent years, we evaluated treatment change and COPD exacerbations, defined as emergency care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for lower respiratory tract infection.Results: Mean patient age was 67 years, 57%-60% being male. For both initiation (n=334:334) and step-up (n=189:189) patients, exacerbation rates were comparable between extrafine beclomethasone and fluticasone cohorts during the 2 year outcome period. Odds of treatment stability (no exacerbation or treatment change) were significantly greater for patients initiating extrafine beclomethasone compared with fluticasone (adjusted odds ratio 2.50; 95% confidence interval, 1.32-4.73). Median ICS dose exposure during 2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone than fluticasone cohorts (315 mu g/day versus 436 mu g/day for initiation, 438 mu g/day versus 534 mu g/day for step-up patients).Conclusion: We observed that small-particle ICS at significantly lower doses had comparable effects on exacerbation rates as larger-particle ICS at higher doses, whereas initiation of small-particle ICS was associated with better odds of treatment stability during 2-years' follow-up.

Background Patterns of health-care use and comorbidities present in patients in the period before diagnosis of chronic obstructive pulmonary disease (COPD) are unknown. We investigated these factors to inform future case-finding strategies.Methods We did a retrospective analysis of a clinical cohort in the UK with data from Jan 1, 1990 to Dec 31, 2009 (General Practice Research Database and Optimum Patient Care Research Database). We assessed patients aged 40 years or older who had an electronically coded diagnosis of COPD in their primary care records and had a minimum of 3 years of continuous practice data for COPD (2 years before diagnosis up to a maximum of 20 years, and 1 year after diagnosis) and at least two prescriptions for COPD since diagnosis. We identified missed opportunites to diagnose COPD from routinely collected patient data by reviewing patterns of health-care use and comorbidities present before diagnosis. We assessed patterns of health-care use in terms of lower respiratory consultations (infective and non-infective), lower respiratory consultations with a course of antibiotics or oral steroids, and chest radiography. If these events did not lead to a diagnosis of COPD, they were deemed to be missed opportunities. This study is registered with ClinicalTrials.gov, number NCT01655667.Findings We assessed data for 38 859 patients. Opportunities for diagnosis were missed in 32 900 (85%) of 38 859 patients in the 5 years immediately preceding diagnosis of COPD; in 12 856 (58%) of 22 286 in the 6-10 years before diagnosis, in 3943 (42%) of 9351 in the 11-15 years before diagnosis; and in 95 (8%) of 1167 in the 16-20 years before diagnosis. Between 1990 and 2009, we noted decreases in the age at diagnosis (0 . 05 years of age per year, 95% CI 0.03-0.07) and yearly frequency of lower respiratory prescribing consultations (rate ratio 0 . 982 opportunities per year, 95% CI 0.979-0.985). Prevalence of all comorbidities present at COPD diagnosis increased except for asthma and bronchiectasis, which decreased between 1990 and 2007, from 281 (33 . 4%) of 842 patients to 451 of 1465 (30 . 8%) for asthma, and from 53 of 842 (6 . 3%) to 53 of 1465 (3 . 6%) for bronchiectasis. In the 2 years before diagnosis, of 6897 patients who had had a chest radiography, only 2296 (33%) also had spirometry.Interpretation Opportunities to diagnose COPD at an earlier stage are being missed, and could be improved by case-finding in patients with lower respiratory tract symptoms and concordant long-term comorbidities.

Background: Extra-fine particle hydrofluoroalkane beclomethasone dipropionate (EF HFA-BDP, QVAR®) results in greater overall lung disposition including the small airways. This study compared outcomes achieved by EF HFA-BDP with or without spacer to those achieved by standard particle fluticasone propionate (FP) with spacer. Methods: Retrospective study using UK Clinical Practice and Optimum Patient Care Research Databases. Patients aged 5-11yrs initiating EF HFA-BDP with or without spacer were matched to patients initiating FP with spacer on baseline demographic and disease characteristics. Outcomes evaluated over 1yr: risk domain asthma control (RDAC-absence of: severe exacerbations, lower respiratory infection and antibiotics, or out-patient/out-of-hours attendance), ATS/ERS defined exacerbations, overall asthma control (RDAC plus short acting beta2 agonists (SABA) use), clinical defined exacerbations, treatment success (asthma control and no change in therapy) and odds of higher SABA use. Results: Cohort consisted of 465 patients initiating EF HFA-BDP (of which 319 were prescribed spacer) and 465 patients initiating FP with spacer. Conclusion: When FP was initiated with a spacer, matched children receiving EF HFA-BDP had better outcomes in most domains assessed.