Studies in progress

1. Studies in progress Studies already under the REG umbrella: David Price

2. REG studies underway • Asthma endpoint validation study • Predictors of asthma risk ­ patient characteristics associated with the “frequent exacerbator phenotype” • Add-on therapy in paediatric asthma • Mortality risk associated with NRT • UK Department of Health collaborations: • Active comorbidities at time of COPD diagnosis • “Missed diagnostic opportunities”: Patterns in healthcare resource utilisations in the years preceding a COPD diagnosis • Trajectories of diagnosis and treatment for obstructive airways disease following patient presentation • Real-life exploration of disease patterns and management approaches in idiopathic pulmonary fibrosis

3. Validation of real-life asthma endpoints • Aim: to validate a series of objective of asthma control measures that have been used in published real-life respiratory research. • The outcome measures will be: • compared and contrasted to patient-reported outcomes and/or gold-standard, validated asthma control tools and measures (as appropriate). • Assessed in terms of their relevance, responsiveness and predictive value • A rank order of outcomes (and possibly hierarchical modelling) will be established to aid in appropriate outcome selection for future studies. • Outcomes to be evaluated include composite and proxy measures of: • Asthma control • Severe exacerbations • Proxies for treatment success (control + no change in therapy) • Hospitalisations • ICS compliance (including medication possession ratio) • Controller-to-reliever ratio • Oral thrush

4. Predictors of asthma risk • Hypothesis: there is a frequent-exacerbation phenotype in asthma that results in increased risk of asthma exacerbations. It may be possible to identify patients with this phenotype using routine data collected in primary care. • Populations of interest: high risk and low risk • Study design: • Phase I: A descriptive analysis of longitudinal patient data. Prescribed oral steroid courses will be mapped for all asthma patients over a 5-year period. • Data will be tabulated for all 5 years, but split by year. • A distribution of oral steroid prescriptions will be produced • Frequent exacerbators within the population will be identified • A similar table will be produced for all acute lower respiratory events to include aggregated steroid courses and antibiotic treated episodes and disaggregated events • Phase II: Investigation of individual patient characteristics associated with the frequent asthma exacerbation phenotype (vs controls) • Phase III: Multivariate modelling to weight individual characteristics and identify a possible composite group of characteristics strongly associated with frequent asthma exacerbations (that could be used to inform a clinical decision support tool)

5. Add-on therapy in paediatric asthma (I) • Objectives: to investigate the relationships between asthma control in paediatric patients and : • Primary: therapy step-up (i.e. addition of LABA, LTRA or ICS dose increase) • Secondary: change in inhaler type (i.e. DPI to MDI, DPI to MDI) • Study population: patients with asthma aged 5–12 years • Outcome period: 12 months • Data cut / study period: Jan 1990–Dec 2010 • Data source: Clinical Practice Research Database (CPRD) & Optimum Patient Care Database (OPCRD) • Outcome measures: Severe exacerbations (ATS/ERS-defined and clinical definition); rate control (risk domain asthma control impairment; treatment success; hospitalisations; adherence to ICS; SABA usage; oral thrush)

6. Mortality risk associated with NRT • Matched cohort study to evaluate cardiovascular disease risk following exposure to pharmacological smoking cessation interventions in a real-life UK primary care population • Exposed patients: • Smokers with no past history of CVD whose first recorded smoking cessation intervention was a cessation attempt assisted by one of the following pharmacological smoking cessation interventions at NRT as any, or a combination, of • transdermal patches • nasal spray • gum and tablets • inhaler • Other pharmacological smoking cessation interventions (e.g. bupropion, varenicline). • Non-exposed patients: smokers with no past history of CVD or prior cessation attempts whose first recorded smoking cessation intervention involved receipt of smoking cessation advice (not pharmacological therapy)

7. Mortality risk associated with NRT • Matched analyses: • Smoking cessation advice vs NRT • NRT vs other pharmacological methods (e.g. bupropion, varenicline) • Smoking cessation advice vs other pharmacological (e.g. bupropion, varenicline) • Outcomes • Primary outcome: CV event during 4-week outcome period • Secondary Outcome: CV event during 52-week outcome period • Tertiary Outcomes: at any time after IPD

8. Active comorbidities at the time of diagnosis of COPD • Background: A collaborative observational study carried out by the UK Department of Health and Research in Real Life collaborative and independent respiratory experts • Presented: ERS, Amsterdam September 2011 • Rationale: Comorbidities can potentiate the morbidity of chronic obstructive pulmonary disease (COPD), and vice versa. Patients with COPD often die as a result of a comorbidities. • Objectives: Evaluate prevalence of comorbidities at COPD diagnosis in real-world patients over a 10-yr period. • Authors: D Price*, R Jones, D Halpin, R Winter, SL Hill, E Bateman, D Freeman, M Kearney, K Holton, A Moger, A Burden, J von Ziegenweidt, L Mascarenhas, A Chisholm, D Ryan

9. Active COPD comorbidities: conclusions (I) • The data confirm that active comorbidities are common at the time of COPD diagnosis. • Trends over the study period suggest: • Constant diagnosis of asthma • Increased prevalence of active comorbidities • Association between presence of comorbidities and milder COPD at time of diagnosis • The increased prevalence of active comorbidities at the time of COPD diagnosis may indicate: • Increased awareness of comorbidities • Improved diagnosis of COPD in patients treated for comorbidities • Effects of national targets, e.g. UK Quality and Outcomes Framework.

10. Active COPD comorbidities: conclusions (II) • Close monitoring of patients with existing conditions present opportunity for earlier COPD identification and diagnosis. • Decision support prompts: • Patients with a positive smoking history and either: • IHD and/or • Diabetes • should be evaluated for presence of COPD as part of their reviews • Integrated, holistic management of patients with COPD (≥GOLD II) is required to optimise care and minimse the morbidity and mortality of patients with COPD (e.g. reduce myocardial infractions and strokes for those COPD patients with comorbid IHD).

11. Missed opportunities to diagnose COPD • Background: A collaborative observational study carried out by the UK Department of Health and Research in Real Life collaborative and independent respiratory experts • Presented: ERS, Amsterdam September 2011 • Rationale: Early diagnosis and intervention in the management of symptomatic chronic obstructive pulmonary disease (COPD) may reduce the associated impact on patients and economic burden on health systems. • Objectives: Characterise healthcare utilisation in the yrs preceding a definitive COPD diagnosis to identify “red flags” that may aid in earlier diagnosis. • Authors: D Price*, R Jones, D Halpin, R Winter, SL Hill, E Bateman, D Freeman, M Kearney, K Holton, A Moger, A Burden, J von Ziegenweidt, L Mascarenhas, A Chisholm, D Ryan

12. Missed opportunities to diagnose COPD: conclusions (I) Opportunities to diagnose COPD are being missed: • In UK primary care • e.g. Chest X-rays rather than spirometry • In secondary care • both in respiratory outpatients and admissions • Further investigations are required on: • Variability of care in the UK • Educational deficits • Key to changing clinical behaviour

13. Missed opportunities to diagnose COPD: conclusions (II) • Be wise before the event • Current work to improve earlier diagnosis includes: • Service evaluations of routinely collected data: remote identification of patients at risk having COPD • Decision support software: identify patterns around respiratory consultations, risk factors and prescribing–prompts assessment automatically generated • Resource assessment: does improvement in early diagnosis justify investment by commissioners

14. Trajectories of diagnosis and treatment for obstructive airways disease • Research team: Hillary Pinnock & Chris Burton, University of Edinburgh • Data source: Optimum Patient Care Research Database (OPCD) • Aim: to map and characterise consultation trajectories from first presentation with respiratory symptoms and for up to three years after diagnosis.

15. Idiopathic pulmonary fibrosis • Research team: Andrew Wilson, University of East Anglia • Data source: Optimum Patient Care Research Database (OPCRD) • Research topics: • Validation work: • Consistency of IPF coding within primary care  • Prevalence • Disease progression and life expectancy • Reflux as a potential cause of IPF: explore the pattern of PPI use • Impact of steroids on infection rates (pneumonia, LRTIs) in IPF • Prognostic power of high neutrophil counts in IPF