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Background Routinely-collected healthcare data provide a valuable resource for epidemiological research. Validation studies have shown that for most conditions, simple lists of clinical codes can reliably be used for case finding in primary care, however, studies exploring the robustness of this approach are lacking for diseases such as idiopathic pulmonary fibrosis (IPF) which are largely managed in secondary care. Method Using the UK’s Clinical Practice Research Datalink (CPRD) Aurum dataset, which comprises patient-level primary care records linked to national hospital admissions and cause-of-death data, we compared the positive predictive value (PPV) of eight diagnostic algorithms. Algorithms were developed based on the literature and IPF diagnostic guidelines using combinations of clinical codes in primary and secondary care (SNOMED-CT or ICD-10) with/without additional information. The positive predictive value (PPV) was estimated for each algorithm using the death record as the gold standard. Utilization of the reviewed codes across the study period was observed to evaluate any change in coding practices over time. Result A total of 17,559 individuals had a least one record indicative of IPF in one or more of our three linked datasets between 2008 and 2018. The PPV of case-finding algorithms based on clinical codes alone ranged from 64.4% (95%CI:63.3–65.3) for a “broad” codeset to 74.9% (95%CI:72.8–76.9) for a “narrow” codeset comprising highly-specific codes. Adding confirmatory evidence, such as a CT scan, increased the PPV of our narrow code-based algorithm to 79.2% (95%CI:76.4–81.8) but reduced the sensitivity to under 10%. Adding evidence of hospitalisation to the standalone code-based algorithms also improved PPV, (PPV = 78.4 vs. 64.4%; sensitivity = 53.5% vs. 38.1%). IPF coding practices changed over time, with the increased use of specific IPF codes. Conclusion High diagnostic validity was achieved by using a restricted set of IPF codes. While adding confirmatory evidence increased diagnostic accuracy, the benefits of this approach need to be weighed against the inevitable loss of sample size and convenience. We would recommend use of an algorithm based on a broader IPF code set coupled with evidence of hospitalisation.

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research.

Background: Asthma-related burden remains poorly characterised in children in the United Kingdom (UK). We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds). Methods: The Clinical Practice Research Datalink Aurum database (2008‒2018) was utilised to assess annual asthma incidence and prevalence in 1‒17-year-olds and pre-school wheeze in 1‒5-year-olds, stratified by gender and age. During the same period, annual asthma exacerbation rates were assessed in those with either a diagnosis of pre-school wheeze or asthma. Results: Annual asthma incidence rates decreased by 51% from 1403.4 (95% confidence interval 1383.7‒1423.2) in 2008 to 688.0 (676.3‒699.9) per 105 person-years (PYs) in 2018, with the most pronounced decrease observed in 1‒5-year-olds (decreasing by 65%, from 2556.9 [2509.8‒2604.7] to 892.3 [866.9‒918.3] per 105 PYs). The corresponding decreases for the 6‒11- and 12‒17-year-olds were 36% (1139.9 [1110.6‒1169.7] to 739.9 [720.5‒759.8]) and 20% (572.3 [550.4‒594.9] to 459.5 [442.9‒476.4]) per 105 PYs, respectively. The incidence of pre-school wheeze decreased over time and was slightly more pronounced in the 1‒3-year-olds than in the 4-year-olds. Prevalence of asthma and pre-school wheeze also decreased over time, from 18.0% overall in 2008 to 10.2% in 2018 for asthma. Exacerbation rates increased over time from 1.33 (1.31‒1.35) per 10 PYs in 2008 to 1.81 (1.78‒1.83) per 10 PYs in 2018. Conclusion: Paediatric asthma incidence decreased in the UK since 2008, particularly in 1– 5-year-olds; this was accompanied by a decline in asthma prevalence. Pre-school wheeze incidence also decreased in this age group. However, exacerbation rates have been increasing.

Background There is considerable variation in reported chronic obstructive pulmonary disease (COPD) prevalence internationally, partly due to differing definitions in use. Accurate estimates of disease prevalence are important for allocation of healthcare resources, yet UK estimates of COPD prevalence have not been updated for a decade. We calculated yearly COPD prevalence in England between 2000 and 2019 using different definitions of COPD. Methods We used routinely collected primary care electronic healthcare record (EHR) data from the Clinical Practice Research Datalink (CPRD) Aurum database linked with secondary care data from the Hospital Episode Statistics (HES) Admitted Patient Care (APC) database. Mid-year point prevalence was calculated yearly from 2000 to 2019 in English adults aged ≥40 years using 5 definitions: (i) validated COPD, (ii) Quality and Outcomes Framework (QOF) COPD, (iii) COPD symptoms, inhaler prescription, and no asthma diagnosis, (iv) hospitalisation with COPD as any diagnosis, (v) hospitalisation with COPD as primary or secondary diagnosis. Prevalence was further stratified by gender, age group, and region. Results 12,745,793 people were included over the 20-year period. Annual cohort sizes ranged from 4,373,538 in 2000 to 6,159,496 in 2019. Estimates of COPD prevalence increased every year from 2000 and the difference in estimated prevalence between the validated and QOF definitions has grown over time. In 2019, a COPD prevalence of 4.9% was found using validated events in either primary or secondary care (definition 1 or definition 5). Additionally including potentially undiagnosed cases (definition 3) in the COPD definition produced an increased prevalence of 6.7%. Conclusion Common definitions of COPD (e.g., QOF codes), may underestimate the true prevalence. The extent of this underestimate has increased over time and could lead to under-allocation of resources where need is estimated based on these definitions. Standardisation of COPD coding in routine EHRs and metrics such as spirometry is key to accurate disease monitoring.

Background Identifying correlates of cause-specific mortality in patients with COPD may aid the targeting of therapies to reduce mortality. We determined factors associated with causes of death in a primary care COPD population. Methods Clinical Practice Research Datalink Aurum was linked to Hospital Episode Statistics and death certificate data. People with COPD alive between 01/01/2010-01/01/2020 were included. Patient characteristics were defined before of follow-up: i) frequency and severity of exacerbations; ii) emphysema or chronic bronchitis; iii) GOLD group A-D; and iv) airflow limitation. We used Cox proportional hazards regression and competing risks to investigate the association between patient characteristics and risk of all-cause, COPD and cardiovascular (CV)-mortality. Results 339,647 people with COPD were included of which 97,882 died during follow-up (25.7% COPD-related and 23.3% CV-related). Airflow limitation, GOLD group, exacerbation frequency and severity, and COPD phenotype were associated with all-cause mortality. Exacerbations, both increased frequency and severity, were associated with COPD-related mortality (≥2 exacerbations vs none HR 1.64, 1.57-1.71; 1 severe vs none 2.17, 2.04-2.31, respectively). Patients in GOLD groups B-D had higher risk of COPD and CV-mortality compared with GOLD A (GOLD D vs A, HR for COPD-mortality 4.57, 4.23-4.93 and HR for CV-mortality 1.53, 1.41-1.65). Increasing airflow limitation was also associated with both COPD and CV-mortality (GOLD 4 vs 1, HR 12.63, 11.82-13.51 and HR 1.75, 1.60-1.91, respectively). Conclusion Poorer airflow limitation, worse functional status, and exacerbations had substantial associations with risk of all-cause mortality. Differing results for CV and COPD-related mortality suggests interventions to prevent mortality may need to target particular characteristics or time points in the disease course.

Background: The British Lung Foundation previously estimated that 2.2 million symptomatic but undiagnosed people with COPD live in the UK. Aim: This study investigates the proportion of patients with a missed COPD diagnosis among those with COPD as the cause of death on their death certificate and how this has changed over the past 17 years. Design and Setting: We linked Clinical Practice Research Datalink Aurum and GOLD primary care data with Office for National Statistics mortality data and Hospital Episode Statistics data. We included adults who died between 2000 and 2017 with COPD as their main cause of death. Method: Using a range of diagnostic COPD criteria, we estimated the proportion of patients with a missed COPD diagnosis, and described the demographic and clinical characteristics of patients with and without prior COPD diagnosis using a mixed effect logistic regression model. Results: Depending on the COPD definition used, between 96% and 27% of the 78,621 patients included received a diagnosis of COPD prior to death. Using presence of a COPD Read or SNOMED CT code and performed spirometry as a main definition, just over half of the patients (52%) had received a COPD diagnosis overall, with a proportion of those who did not decreasing from 91% in 2000 to 31% in 2017 (p-trend

Rationale: Differences in clinical presentation and outcomes between HF phenotypes in patients with COPD have not been assessed. Objectives: The aim of this study was to compare clinical outcomes and healthcare resource use (HRU) between patients with COPD and HF with preserved (HFpEF), mildly-reduced (HFmrEF), and reduced ejection fraction (HFrEF). Methods: Patients with COPD and HF were identified in the United States (US) administrative claims database OptumLabs® DataWarehouse between 2008-2018. All-cause and cause-specific (HF) hospitalization, acute exacerbation of COPD (AECOPD, severe and moderate combined), mortality and HRU were compared between HF phenotypes. Results: From 5,419 patients with COPD, 70% had HFpEF, 20% had HFrEF and 10% had HFmrEF. All-cause hospitalization did not differ across groups, however patients with COPD and HFrEF had a greater risk of HF-specific hospitalization (HR 1.54, 95%CI 1.29-1.84) and mortality (HR: 1.17, 95%CI 1.03-1.33) compared to patients with COPD and HFpEF. Conversely, patients with COPD and HFrEF had a lower risk of AECOPD compared with those with COPD and HFpEF (HR 0.75, 95%CI 0.66-0.87). Rates of long-term stays (in skilled-nursing facilities) and emergency room visits were lower for those with COPD and HFrEF than for those with COPD and HFpEF. Conclusion: Outcomes in patients with comorbid COPD and HFpEF are largely driven by COPD. Given the paucity in treatments for HFpEF, better differentiation between cardiac and respiratory symptoms may provide an opportunity to reduce the risk of AECOPD. Risk of death and HF hospitalization were highest among patients with COPD and HFrEF, emphasizing the importance of optimizing guideline-recommended HFrEF therapies in this group.

Objective To describe GP consultation rates for post-COVID-19 sequelae in non-hospitalised and hospitalised COVID-19 patients, and among non-hospitalised individuals describe how GP consultation rates for post-COVID-19 sequelae change over time, as well as following COVID-19 vaccination. Design Population-based cohort study. Setting 1,392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database. Participants 456,002 COVID-19 cases diagnosed between 1st August 2020 to 14th February2021 (44.7% male; median age 61 years), either hospitalised within two weeks of diagnosis or not hospitalised and followed-up for a maximum of 9.2 months. A negative control group of individuals without COVID-19 (N=38,511) and patients with influenza before the pandemic (N=21,803) were used to contextualise findings. Main outcome measures Comparison of GP consultation rates for new symptoms, diseases, prescriptions and healthcare utilisation (HCU) in hospitalised and non-hospitalised individuals separately pre and post-COVID-19 infection using Cox regression and negative binomial regression for HCU. This was repeated for the negative control and influenza cohorts. In non-hospitalised individuals, outcomes were additionally described over time following COVID-19 diagnosis and compared pre and post-COVID-19 vaccine in individuals who were symptomatic post-COVID-19, using negative binomial regression. Results Relative to the negative control and influenza cohorts non-hospitalised patients (N=437,943) had significantly higher GP consultation rates for multiple sequelae, the most common being loss of smell/taste (HRadj 5.28 [95%CI 3.89 to 7.17]; p

Reporting participant ethnicity and socioeconomic status (SES) in clinical research is needed for interpretation and to inform discussion around health inequalities. We assessed the frequency of reporting of ethnicity (or ‘race’) and SES indicators in a sample of 100 research articles, in which participant level are reported, published in the 10 highest impact general medical journals in Spring 2021. 35 reported ethnicity and 13 SES, while 99 reported age, and 97 reported sex or gender. Among the articles not reporting ethnicity only 3(5%) highlighted this as a limitation, and only 6(7%) where SES data were missing. Median number of articles reporting ethnicity per journal was 2.5/10 (range 0-9). In conclusion, reporting of research participant ethnicity and socioeconomic status in high-impact medical journals remains poor, and this omission is rarely acknowledged as a limitation. This situation persists despite the well-established importance of this issue. Standardized explicit minimum standards are required.

Summary report on the views of members of the public on real world evidence studies undertaken as part of building the digital healthcare programme of research in North West London

Objectives To investigate the experience of people who continue to be unwell after acute COVID-19, often referred to as ‘long COVID’, both in terms of their symptoms and their interactions with healthcare. Design We conducted a mixed-methods analysis (quantitative and qualitative) of responses to a survey accessed through a UK online post-COVID support and information hub between April 2020 and December 2020 about people’s experiences after having acute COVID-19. Participants Of 3290 respondents, 78% were female, median age range 45-54 years, 92.1% reported white ethnicity; 12.7% had been hospitalised. 494 respondents (16.5%) completed the survey between 4 and 8 weeks of the onset of their symptoms, 641 (21.4%) between 8 and 12 weeks and 1865 (62.1%) more than 12 weeks after. Results The ongoing symptoms most frequently reported were; breathing problems (92.1%), fatigue (83.3%), muscle weakness or joint stiffness (50.6%), sleep disturbances (46.2%), problems with mental abilities (45.9%) changes in mood, including anxiety and depression (43.1%) and cough (42.3%). Symptoms did not appear to be related to the severity of the acute illness or to the presence of pre-existing medical conditions. Analysis of free text responses revealed three main themes (1) Experience of living with COVID-19 – physical and psychological symptoms that fluctuate unpredictably; (2) Interactions with healthcare; (3) Implications for the future – their own condition, society and the healthcare system and the need for research Conclusion People living with persistent problems after the acute phase of COVID-19 report multiple and varying symptoms that are not necessarily associated with initial disease severity or the presence of pre-existing health conditions. Many have substantial unmet needs and experience barriers to accessing healthcare. Consideration of patient perspective and experiences will assist in the planning of services to address this. Ethical approval Ethical approval was granted by Imperial College Research and Integrity Team (IREC; 20IC6625).

Data promising effective Covid-19 vaccines have accelerated the UK’s mass vaccination programme. The UK public’s attitudes to the government’s prioritisation list are unknown, and achieving critical population immunity will require the remaining majority to accept both vaccination and the delay in access of up to a year or more. This cross-sectional observational study sent an online questionnaire to registrants of the UK National Health Service’s largest personal health record. Question items covered willingness for Covid-19 vaccine uptake and attitudes to prioritisation. Among 9,122 responses, 71.5% indicated wanting a vaccine, below what previous modelling indicated as critical levels for progressing towards herd immunity. 22.7% disagreed with the prioritisation list, though 70.3% were against being able to expedite vaccination through payment. Age and female gender were, respectively, strongly positively and negatively associated with wanting a vaccine. Teachers and Black, Asian and Minority Ethnic (BAME) groups were most cited by respondents for prioritisation. This study identifies factors to inform the public health messaging critical to improving uptake.

Rationale: Heart failure (HF) is a common comorbidity in the chronic obstructive pulmonary disease (COPD) population, but previous research has shown under recognition. Objectives: To determine the incidence of HF in a prevalent COPD cohort. To determine the association of incident HF with short- and long-term mortality of patients with COPD. Methods: Crude incidence of HF in the HF-naïve primary care COPD population was calculated for each year from 2006-2016 using UK data from the Clinical Practice Research Datalink (CPRD). Patients with COPD were identified using a validated code list and were required to be over 35 years old at COPD diagnosis, have a history of smoking, and have documented airflow obstruction. Office of National Statistics provided mortality data for England. Adjusted mortality rate ratios (aMRR) from Poisson regression were calculated for patients with COPD and incident HF (COPD-iHF) in 2006, 2011, and 2015 and compared temporally with patients with COPD and without incident HF (COPD-no HF) in those years. Regression was adjusted for age, sex, BMI, severity of airflow limitation, smoking status, history of cardiovascular disease, and diabetes. Results: We identified 95,987 HF-naïve patients with COPD. Crude incidence of HF was steady from 2006-2016 (1.18 per 100 person-years (95%CI: 1.09, 1.27)). Patients with COPD-iHF experienced greater than threefold increase in one-year mortality and twofold increase in five-year and 10-year mortality compared with patients with COPD-no HF, with no change based on year of HF diagnosis. Mortality of patients with COPD-iHF did not improve over time, comparing incident HF in 2011 (1-year aMRR 1.26, 95%CI: 0.83, 1.90; 5-year aMRR 1.26, 95%CI: 0.98, 1.61) and 2015 (1-year aMRR 1.63, 95%CI: 0.98, 2.70) with incident HF in 2006. Conclusions: The incidence of HF in the UK COPD population was stable in the last decade. Survival of patients with COPD and incident HF has not improved over time in England. Bespoke guidelines for the diagnosis and management of HF in the COPD population are needed to improve identification and survival of patients.

Oral corticosteroids (OCS) are used to manage asthma exacerbations and severe, uncontrolled asthma, but OCS use is associated with adverse effects. We aimed to describe the patterns of OCS use in the real-world management of patients with asthma in western Europe. We used electronic medical records from databases in France, Germany, Italy, and the United Kingdom from July 2011 through February 2018. Patients aged ≥12 years with an asthma diagnosis, ≥1 non-OCS asthma medication within ±6 months of diagnosis, and available data ≥6 months prior to and ≥90 days after cohort entry were included. High OCS use was defined as OCS ≥450 mg prescribed in a 90-day window during follow-up. Baseline characteristics and OCS use during follow-up were described overall and by OCS use status. Of 702 685 patients with asthma, 14–44% were OCS users and 6–9% were high OCS users at some point during follow-up. Annual prevalence of high OCS use across all countries was approximately 3%. High OCS users had a mean 1–3 annual OCS prescriptions, with an average daily OCS dosage of 1.3–2.2 mg. For patients who continued to meet the high use definition, daily OCS exposure was generally stable at 5.5–7.5 mg for at least 2 years, increasing the risk of adverse effects. Our study demonstrates that OCS use is relatively common across the four studied European countries. Data from this study may provide decisive clinical insights to inform primary care physicians and specialists involved in the management of severe, uncontrolled asthma.

Objectives: To characterize peak cardiac troponin levels, in patients presenting with acute myocardial infarction (AMI), according to their comorbid condition and determine the influence of peak troponin (cTn) levels on mortality. Methods: We included patients with the first admission for AMI in the United Kingdom. We used linear regression to estimate the association between eight common co-morbidities {diabetes mellitus(DM), previous angina, peripheral arterial disease(PAD), previous myocardial infarction(MI), chronic kidney disease(CKD), cerebrovascular disease(CVD), chronic heart failure(CHF), and chronic obstructive pulmonary disease(COPD)} and peak cTn. Peak cTn levels were adjusted for age, sex, smoking status and co-morbidities. Logistic regression and restricted cubic spline models were employed to investigate the association between peak cTn and 180-day mortality for each co-morbidity. Results: 330,367 patients with AMI were identified. Adjusted peak cTn levels were significantly higher in patients with CKD[adjusted % difference in peak cTnT for CKD=42%, 95%CI 13.1 to 78.4] and significantly lower for patients with COPD, previous angina, previous MI and CHF when compared to patients without the respective co-morbidities (reference group) [cTnI;COPD=-21.7%,95%CI -29.1 to -13.4;previous angina=-24.2%, 95%CI -29.6 to -8.3;previous MI=-13.5%, 95%CI -20.6 to -5.9;CHF=-28% 95%CI -37.2 to -17.6]. Risk of 180-day mortality in most of the co-morbidities did not change substantially after adjusting for peak cTn. In general, cTnI had a stronger association with mortality than cTnT. Conclusions: In this nationwide analyses of patients presenting with acute myocardial infarction, co-morbidities substantially influenced systemic concentrations of peak cTn. Comorbid illness is a significant predictor of mortality regardless of peak cTn levels and should be taken into consideration while interpreting cTn both as a diagnostic and prognostic biomarker.

Rate of FEV1 decline in COPD is heterogeneous and the extent to which inhaled corticosteroids (ICS) influence the rate of decline is unclear. The majority of previous reviews have investigated specific ICS and non-ICS inhalers and have consisted of randomised control trials (RCTs), which have specific inclusion and exclusion criteria and short follow up times. We aimed to investigate the association between change in FEV1 and ICS-containing medications in COPD patients over longer follow up times. MEDLINE and EMBASE were searched and literature comparing change in FEV1 in COPD patients taking ICS-containing medications with patients taking non-ICS-containing medications were identified. Titles, abstract, and full texts were screened and information extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool and a descriptive synthesis of the literature was carried out due to the heterogeneity of included studies. 17 studies met our inclusion criteria. We found that the difference in change in FEV1 in people using ICS and non-ICS containing medications depended on the study follow-up time. Shorter follow-up studies (1 year or less) were more likely to report an increase in FEV1 from baseline in both patients on ICS and in patients on non-ICS-containing medications, with the majority of these studies showing a greater increase in FEV1 in patients on ICS-containing medications. Longer follow-up studies (greater than 1 year) were more likely to report a decline in FEV1 from baseline in patients on ICS and in patients on non-ICS containing medications but differences between rates of FEV1 of decline were not significant. Further studies are needed to better understand changes in FEV1 when ICS-containing medications are prescribed and to determine whether ICS-containing medications influence rate of decline in FEV1 in the long term. Results from inclusive trials and observational patient cohorts may provide information more generalisable to a population of COPD patients.

Background Although lung volume reduction surgery (LVRS) improves survival in appropriately selected patients with Chronic Obstructive Pulmonary Disease (COPD), few procedures are performed. The National Institute for Clinical and Healthcare Excellence recently recommended a more systematic approach to identifying potential candidates. We investigated LVRS referrals from a UK primary care population and aimed to establish an accurate estimate of eligible patients and determine a strategy for identifying potential candidates systematically. Methods Clinical Practice Research Datalink (CPRD) GOLD (a primary care database), linked Hospital Episode Statistics (HES) inpatient and Diagnostic Imaging Dataset (DID) were used. COPD patients who had undergone LVRS, patients who met basic eligibility criteria for further screening for LVRS, and patients meeting a more stringent eligibility criteria were identified from April 2012 to September 2015. Thoracic CT, pulmonary rehabilitation status, referral to respiratory outpatient clinics, and AECOPD requiring hospitalisation were compared between actual LVRS recipients and potentially eligible patients. Results Among 73,697 COPD patients included, 36 (0.05%) received LVRS, 5,984 (8.1%) met basic eligibility criteria, and 159 (0.2%) met more stringent eligibility criteria. LVRS recipients were younger (mean(SD) age: 64(9.2) years) compared to the stringently eligible patients (69(8.9) years) (p=0.01). Few patients meeting stringent eligibility criteria (6.9%) had a CT thorax in the preceding 3 years or been referred for assessment in secondary care. Conclusions A substantial unmet need exists among COPD patients who could potentially benefit from a lung volume reduction procedure but who are not being investigated or referred to consider this possibility.

Background Chronic obstructive pulmonary disease (COPD) is a major cause of mortality. Patients with advanced disease often have a poor quality of life, such that guidelines recommend providing palliative care in their last year of life. Uptake and use of palliative care in advanced COPD is low; difficulty in predicting 1-year mortality is thought to be a major contributing factor. Methods We identified two primary care COPD cohorts using UK electronic healthcare records (Clinical Practice Research Datalink). The first cohort was randomised equally into training and test sets. An external dataset was drawn from a second cohort. A risk model to predict mortality within 12 months was derived from the training set using backwards elimination Cox regression. The model was given the acronym BARC based on putative prognostic factors including body mass index and blood results (B), age (A), respiratory variables (airflow obstruction, exacerbations, smoking) (R) and comorbidities (C). The BARC index predictive performance was validated in the test set and external dataset by assessing calibration and discrimination. The observed and expected probabilities of death were assessed for increasing quartiles of mortality risk (very low risk, low risk, moderate risk, high risk). The BARC index was compared to the established index scores body mass index, obstructive, dyspnoea and exacerbations (BODEx), dyspnoea, obstruction, smoking and exacerbations (DOSE) and age, dyspnoea and obstruction (ADO). Results Fifty-four thousand nine hundred ninety patients were eligible from the first cohort and 4931 from the second cohort. Eighteen variables were included in the BARC, including age, airflow obstruction, body mass index, smoking, exacerbations and comorbidities. The risk model had acceptable predictive performance (test set: C-index = 0.79, 95% CI 0.78–0.81, D-statistic = 1.87, 95% CI 1.77–1.96, calibration slope = 0.95, 95% CI 0.9–0.99; external dataset: C-index = 0.67, 95% CI 0.65–0.7, D-statistic = 0.98, 95% CI 0.8–1.2, calibration slope = 0.54, 95% CI 0.45–0.64) and acceptable accuracy predicting the probability of death (probability of death in 1 year, n high-risk group, test set: expected = 0.31, observed = 0.30; external dataset: expected = 0.22, observed = 0.27). The BARC compared favourably to existing index scores that can also be applied without specialist respiratory variables (area under the curve: BARC = 0.78, 95% CI 0.76–0.79; BODEx = 0.48, 95% CI 0.45–0.51; DOSE = 0.60, 95% CI 0.57–0.61; ADO = 0.68, 95% CI 0.66–0.69, external dataset: BARC = 0.70, 95% CI 0.67–0.72; BODEx = 0.41, 95% CI 0.38–0.45; DOSE = 0.52, 95% CI 0.49–0.55; ADO = 0.57, 95% CI 0.54–0.60). Conclusion The BARC index performed better than existing tools in predicting 1-year mortality. Critically, the risk score only requires routinely collected non-specialist information which, therefore, could help identify patients seen in primary care that may benefit from palliative care.

Introduction Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory conditions, which result in significant morbidity worldwide. These conditions are associated with a range of non-specific symptoms, which in themselves are a target for health research. Such research is increasingly being conducted using electronic health records (EHRs), but computable phenotype definitions, in the form of code sets or code lists, are required to extract structured data from these large routine databases in a systematic and reproducible way. The aim of this protocol is to specify a systematic review to identify code sets for respiratory symptoms in EHRs research. Methods and analysis MEDLINE and Embase databases will be searched using terms relating to EHRs, respiratory symptoms and use of code sets. The search will cover all English-language studies in these databases between January 1990 and December 2017. Two reviewers will independently screen identified studies for inclusion, and key data will be extracted into a uniform table, facilitating cross-comparison of codes used. Disagreements between the reviewers will be adjudicated by a third reviewer. This protocol has been produced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines. Ethics and dissemination As a review of previously published studies, no ethical approval is required. The results of this review will be submitted to a peer-reviewed journal for publication and can be used in future research into respiratory symptoms that uses electronic healthcare databases.

Introduction Chronic obstructive pulmonary disease (COPD) exacerbations progress the course of disease and impair lung function. Inhaled maintenance therapy reduces exacerbations. It is not yet established which inhaled therapy combination is best to reduce exacerbations, lung function decline and symptom burden. Methods and analysis MEDLINE, EMBASE and the Cochrane Library will be searched for articles between January 2011 and May 2018 using a pre-specified search strategy. Conference proceedings will be searched. Systematic reviews (with or without meta-analysis), randomised controlled trials (RCTs), cohort studies and case controlled studies comparing six interventions comprising different combinations of long-acting bronchodilators and inhaled corticosteroids in unison or on their own. The primary outcome is the reduction in moderate-to-severe exacerbations. Secondary outcomes include: lung function, quality of life, mortality and other adverse events. Titles and abstracts will screened by the primary researcher. A second reviewer will repeat this on a proportion of records. The Population, Intervention, Comparator, Outcomes and Study framework will be used for data extraction. A network meta-analyses of outcomes from RCTs and real-world evidence will be integrated if feasible. The 95% credible interval will be used to assess the statistical significance of each summary effect. Ranking of interventions will be based on their surface under cumulative ranking area. Ethics and dissemination COPD exacerbations are burdensome to patients. We aim to report results that provide clinicians with a more informed choice of which inhaled therapy combinations are best to reduce exacerbations, improve disease burden and reduce lung function and exercise capacity decline, compared with the potential harms, in certain populations with COPD.

Background People with chronic obstructive pulmonary disease (COPD) are at increased risk of vascular disease, including venous thromboembolism (VTE).1 While some researchers have tested the hypothesis that within COPD certain subgroups of patients, in particular frequent exacerbators, are at even greater risk of cardiovascular disease, no large-scale investigations of the relationship between exacerbation frequency or disease severity and VTE risk have been undertaken. Methods 3,594 COPD patients recording a first VTE event during the period 1 January 2004 to 31 December 2013 were identified from the Clinical Practice Research Datalink (CPRD GOLD) dataset (cases) and matched (1:3) on age, sex and GP practice to 10,782 VTE-free COPD patients (controls). COPD severity was categorised by degree of airflow limitation (i.e. GOLD stage) and by COPD medication history (very severe, severe, moderate/mild). Patients were classed as “frequent exacerbators” if they experienced ≥ 2 exacerbations per year and as “infrequent exacerbators” otherwise. Analyses were conducted in STATA using conditional logistic regression to account for the study design. Results After controlling for smoking and BMI, as well as the matching variables, there was an association between increased disease severity and VTE when severity was measured in terms of lung function impairment (ORmoderate/mild = 1.16; 95% CIs: 1.03, 1.32; p = 0.018) and also in terms of medication history (ORsevere/moderate+mild = 1.17; 95% CIs: 1.06, 1.26; p = 0.001). There was no evidence to suggest that that frequent exacerbators were at greater risk of VTE than infrequent exacerbators (OR = 1.06; 95%: CIs 0.97, 1.15; p = 0.18). Conclusion Severity of disease but not frequent exacerbation appears to be associated with VTE events in COPD patients.

Chronic obstructive pulmonary disease (COPD), is associated with an increased risk of\ud myocardial infarction (MI), and additionally, cardiovascular disease is responsible for up to 1/3\ud of deaths in people with COPD. This may be attributable to the fact people with COPD are\ud managed differently and have higher mortality after MI compared to people without COPD.\ud One reason for the differences in management may be that prognostic risk scores after MI do\ud not perform well in those with COPD. Another reason may be that acute exacerbations of\ud COPD (AECOPD) are thought to be associated with a transiently increased risk of MI.\ud The aims of this thesis are to: 1)systematically review the evidence for an increased risk of MI\ud associated with COPD and AECOPD, and increased risk of death following MI for those with\ud COPD; 2) investigate the potential contribution of differences in management after MI on\ud differences in mortality; 3) investigate the performance of prognostic risk scores after MI for\ud those with COPD; 4) validate the recording of AECOPD in UK electronic healthcare records\ud (EHR); 5) investigate the recording of hospitalisations for AECOPD in UK primary and\ud secondary care EHR; and 6) to conduct a self-controlled case series to investigate the risk of MI\ud associated with AECOPD.\ud This work showed an increased risk of MI associated with COPD independent of smoking, and\ud evidence for an increased risk of death following hospital discharge for people with compared\ud to those without COPD.\ud This work demonstrated that differences in recognition and management of MI for those with\ud COPD may explain some of the higher risk of death for COPD patients following MI.\ud Additionally, the GRACE score (commonly used for risk stratification following MI) does not\ud perform as well for COPD patients and may explain some of the differences in management.\ud A validated algorithm was developed for identifying AECOPD both in primary care and\ud resulting in hospital admission in electronic health records.\ud Finally, using a self-controlled case series analysis, data showed that AECOPD is associated\ud with increased risk of MI for approximately four weeks following AECOPD onset, and that the\ud risk is modified by important patient characteristics.