Defining the relationship between COPD and CVD: what are the implications for clinical practice?

Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD). CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality. The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself. Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade. But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population. The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors. In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence. We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD. While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years. Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective

Nontuberculous mycobacterial disease managed within UK primary care, 2006-2016

Previous UK studies investigating nontuberculous mycobacteria have been limited to reporting isolation from culture, not burden of disease. We assessed the burden of nontuberculous mycobacterial disease (NTMD) in UK primary care from 2006 to 2016. Using electronic healthcare records, we identified patients with NTMD using a strict definition including patients with guideline-directed treatment/monitoring. We described treatment regimens and incidence/prevalence in the general population and in patients with underlying chronic respiratory diseases. Incidence of primary care-managed NTMD in the general population decreased (2006 to 2016 rates per 100,000 person-years, 3.85 to 1.28). Average annual prevalence of NTMD in the general population was 6.38 per 100,000. Around 85% were taking antimycobacterial therapy; 53.2% were taking a guideline-recommended regimen. Incidence of NTMD in patients with respiratory disease decreased (2006 to 2016 rates per 100,000 person-years, 12.5 to 7.40). Average annual prevalence of NTMD in patients with respiratory disease was 27.7 per 100,000. This is the first UK study using nationally representative data to investigate the burden of NTMD managed within primary care. Incidence and prevalence of managed NTMD within primary care is gradually declining. Increasing complexity in the management of NTMD may be driving a shift in care to secondary settings

Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)

Objectives: The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. Setting: 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. Primary outcome measure: The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. Results: 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%). Conclusions: Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004

Does pay-for-performance improve patient outcomes in acute exacerbation of COPD admissions?

BACKGROUND: The COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD. METHODS: Longitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission. RESULTS: 28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81)). CONCLUSION: Completion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions

Do influenza and pneumococcal vaccines prevent community-acquired respiratory infections among older people with diabetes and does this vary by chronic kidney disease? A cohort study using electronic health records

Objective: We aimed to estimate the effectiveness of influenza and 23-valent pneumococcal polysaccharide vaccination on reducing the burden of community-acquired lower respiratory tract infection (LRTI) among older people with diabetes, and whether this varied by chronic kidney disease status. Research design and methods: We used linked UK electronic health records for a retrospective cohort study of 190,492 patients ≥65 years with diabetes mellitus and no history of renal replacement therapy, 1997–2011. We included community-acquired LRTIs managed in primary or secondary care. Infection incidence rate ratios were estimated using Poisson regression. Pneumococcal vaccine effectiveness (VE) was calculated as (1 – effect measure). To estimate influenza VE a ratio-of-ratios analysis (winter effectiveness/summer effectiveness) was used to address confounding by indication. Final VE estimates were stratified according to estimated glomerular filtration rate and proteinuria status. Results: Neither influenza nor pneumococcal vaccine uptake varied according to CKD status. Pneumococcal VE was 22% (95%CI: 11–31) against community-acquired pneumonia for the first year after vaccination, but was negligible after five years. In the ratio-of-ratios analysis, current influenza vaccination had 7% effectiveness for preventing community-acquired LRTI (95%CI: 3–12). Pneumococcal vaccine effectiveness was lower among patients with a history of proteinuria than among patients without proteinuria (p=0.04), but otherwise this study did not identify variation in pneumococcal or influenza VE by markers of CKD. Conclusions: The public health benefits of influenza vaccine may be modest among older people with diabetes. Pneumococcal vaccination protection against community-acquired pneumonia declines swiftly: alternative vaccination schedules should be investigated

External validation of ADO, DOSE, COTE and CODEX at predicting death in primary care patients with COPD using standard and machine learning approaches

Background Several models for predicting the risk of death in people with chronic obstructive pulmonary disease (COPD) exist but have not undergone large scale validation in primary care. The objective of this study was to externally validate these models using statistical and machine learning approaches. Methods We used a primary care COPD cohort identified using data from the UK Clinical Practice Research Datalink. Age-standardised mortality rates were calculated for the population by gender and discrimination of ADO (age, dyspnoea, airflow obstruction), COTE (COPD-specific comorbidity test), DOSE (dyspnoea, airflow obstruction, smoking, exacerbations) and CODEX (comorbidity, dyspnoea, airflow obstruction, exacerbations) at predicting death over 1–3 years measured using logistic regression and a support vector machine learning (SVM) method of analysis. Results The age-standardised mortality rate was 32.8 (95%CI 32.5–33.1) and 25.2 (95%CI 25.4–25.7) per 1000 person years for men and women respectively. Complete data were available for 54879 patients to predict 1-year mortality. ADO performed the best (c-statistic of 0.730) compared with DOSE (c-statistic 0.645), COTE (c-statistic 0.655) and CODEX (c-statistic 0.649) at predicting 1-year mortality. Discrimination of ADO and DOSE improved at predicting 1-year mortality when combined with COTE comorbidities (c-statistic 0.780 ADO + COTE; c-statistic 0.727 DOSE + COTE). Discrimination did not change significantly over 1–3 years. Comparable results were observed using SVM. Conclusion In primary care, ADO appears superior at predicting death in COPD. Performance of ADO and DOSE improved when combined with COTE comorbidities suggesting better models may be generated with additional data facilitated using novel approaches

Acute kidney injury in stable COPD and at exacerbation.

BACKGROUND: While acute kidney injury (AKI) alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known. METHODS: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics) in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107) and identified confounding factors. RESULTS: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03) increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free. CONCLUSION: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome

National clinical audit for hospitalised exacerbations of COPD

Introduction: Exacerbations of COPD requiring hospital admission are burdensome to patients and health services. Audit enables benchmarking performance between units and against national standards, and supports quality improvement. We summarise 23 years of UK audit for hospitalised COPD exacerbations to better understand which features of audit design have had most impact. / Method: Pilot audits were performed in 1997 and 2001, with national cross-sectional audits in 2003, 2008 and 2014. Continuous audit commenced in 2017. Overall, 96% of eligible units took part in cross-sectional audit, 86% in the most recent round of continuous audit. We synthesised data from eight rounds of national COPD audit. / Results: Clinical outcomes were observed to change at the same time as changes in delivery of care: length of stay halved from 8 to 4 days between 1997 and 2014, alongside wider availability of integrated care. Process indicators did not generally improve with sequential cross-sectional audit. Under continuous audit with quality improvement support, process indicators linked to financial incentives (early specialist review (55–66%) and provision of a discharge bundle (53–74%)) improved more rapidly than those not linked (availability of spirometry (40–46%) and timely noninvasive ventilation (21–24%)). / Conclusion: Careful piloting and engagement can result in successful roll-out of cross-sectional national audit in a high-burden disease. Audit outcome measures and process indicators may be affected by changes in care pathways. Sequential cross-sectional national audit alone was not generally accompanied by improvements in care. However, improvements in process indicators were seen when continuous audit was combined with quality improvement support and, in particular, financial incentives

National clinical audit for hospitalised exacerbations of COPD

Introduction: Exacerbations of COPD requiring hospital admission are burdensome to patients and health services. Audit enables benchmarking performance between units and against national standards, and supports quality improvement. We summarise 23 years of UK audit for hospitalised COPD exacerbations to better understand which features of audit design have had most impact. Method: Pilot audits were performed in 1997 and 2001, with national cross-sectional audits in 2003, 2008 and 2014. Continuous audit commenced in 2017. Overall, 96% of eligible units took part in cross-sectional audit, 86% in the most recent round of continuous audit. We synthesised data from eight rounds of national COPD audit. Results: Clinical outcomes were observed to change at the same time as changes in delivery of care: length of stay halved from 8 to 4 days between 1997 and 2014, alongside wider availability of integrated care. Process indicators did not generally improve with sequential cross-sectional audit. Under continuous audit with quality improvement support, process indicators linked to financial incentives (early specialist review (55-66%) and provision of a discharge bundle (53-74%)) improved more rapidly than those not linked (availability of spirometry (40-46%) and timely noninvasive ventilation (21-24%)). Conclusion: Careful piloting and engagement can result in successful roll-out of cross-sectional national audit in a high-burden disease. Audit outcome measures and process indicators may be affected by changes in care pathways. Sequential cross-sectional national audit alone was not generally accompanied by improvements in care. However, improvements in process indicators were seen when continuous audit was combined with quality improvement support and, in particular, financial incentives

The impact of the Covid-19 pandemic on uptake of influenza vaccine: a UK-wide observational study.

BACKGROUND: In the face of the Covid-19 pandemic, the UK National Health Service (NHS) flu vaccination eligibility is extended this season to ~32.4 million (48.8%) of the population. Knowing intended uptake will inform supply and public health messaging to maximise vaccination. OBJECTIVE: The objective of this study was to measure the impact of the Covid-19 pandemic on acceptance of flu vaccination in the 2020-21 season, specifically focusing on those previously eligible who routinely decline vaccination and the newly eligible. METHODS: Intention to receive influenza vaccine in 2020-21 was asked of all registrants of the NHS's largest electronic personal health record by online questionnaire on 31st July 2020. Of those who were either newly or previously eligible but had not previously received influenza vaccination, multivariable logistic regression and network diagrams were used to examine reasons to have or decline vaccination. RESULTS: Among 6,641 respondents, 945 (14.2%) were previously eligible but not vaccinated, of whom 536 (56.7%) intended to receive flu vaccination in 2020/21, as did 466 (68.6%) of the newly eligible. Intention to receive the flu vaccine was associated with increased age, index of multiple deprivation (IMD) quintile, and considering oneself at high risk from Covid-19. Among those eligible but intending not to be vaccinated in 2020/21, 164 (30.2%) gave misinformed reasons. 47 (49.9%) of previously unvaccinated healthcare workers would decline vaccination in 2020/21. CONCLUSIONS: In this sample, Covid-19 has increased acceptance of flu vaccination in those previously eligible but unvaccinated and motivates substantial uptake in the newly eligible. This study is essential for informing resource planning and the need for effective messaging campaigns to address negative misconceptions, also necessary for Covid-19 vaccination programmes. CLINICALTRIAL: Not applicable