Completeness, agreement, and representativeness of ethnicity recording in the United Kingdom's Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES).

BACKGROUND: This descriptive study assessed the completeness, agreement, and representativeness of ethnicity recording in the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) primary care databases alone and, for those patients registered with a GP in England, when linked to secondary care data from Hospital Episode Statistics (HES). METHODS: Ethnicity records were assessed for all patients in the May 2021 builds of the CPRD GOLD and CPRD Aurum databases for all UK patients. In analyses of the UK, English data was from combined CPRD-HES, whereas data from Northern Ireland, Scotland, and Wales drew from CPRD only. The agreement of ethnicity records per patient was assessed within each dataset (CPRD GOLD, CPRD Aurum, and HES datasets) and between datasets at the highest level ethnicity categorisation ('Asian', 'black', 'mixed', 'white', 'other'). Representativeness was assessed by comparing the ethnic distributions at the highest-level categorisation of CPRD-HES to those from the Census 2011 across the UK's devolved administrations. Additionally, CPRD-HES was compared to the experimental ethnic distributions for England and Wales from the Office for National Statistics in 2019 (ONS2019) and the English ethnic distribution from May 2021 from NHS Digital's General Practice Extraction Service Data for Pandemic Planning and Research with HES data linkage (GDPPR-HES). RESULTS: In CPRD-HES, 81.7% of currently registered patients in the UK had ethnicity recorded in primary care. For patients with multiple ethnicity records, mismatched ethnicity within individual primary and secondary care datasets was < 10%. Of English patients with ethnicity recorded in both CPRD and HES, 93.3% of records matched at the highest-level categorisation; however, the level of agreement was markedly lower in the 'mixed' and 'other' ethnic groups. CPRD-HES was less proportionately 'white' compared to the UK Census 2011 (80.3% vs. 87.2%) and experimental ONS2019 data (80.4% vs. 84.3%). CPRD-HES was aligned with the ethnic distribution from GDPPR-HES ('white' 80.4% vs. 80.7%); however, with a smaller proportion classified as 'other' (1.1% vs. 2.8%). CONCLUSIONS: CPRD-HES has suitable representation of all ethnic categories with some overrepresentation of minority ethnic groups and a smaller proportion classified as 'other' compared to the UK general population from other data sources. CPRD-HES data is useful for studying health risks and outcomes in typically underrepresented groups.

Relationship between heart failure and the risk of acute exacerbation of COPD.

RATIONALE: Heart failure (HF) management in chronic obstructive pulmonary disease (COPD) is often delayed or suboptimal. OBJECTIVES: To examine the effect of HF and HF medication use on moderate-to-severe COPD exacerbations. METHODS AND MEASUREMENTS: Retrospective cohort studies from 2006 to 2016 using nationally representative English primary care electronic healthcare records linked to national hospital and mortality data. Patients with COPD with diagnosed and possible HF were identified. Possible HF was defined as continuous loop diuretic use in the absence of a non-cardiac indication. Incident exposure to HF medications was defined as ≥2 prescriptions within 90 days with no gaps >90 days during ≤6 months of continuous use; prevalent exposure as 6+ months of continuous use. HF medications investigated were angiotensin receptor blockers, ACE inhibitors, beta-blockers, loop diuretics and mineralocorticoid receptor antagonists. Cox regression, stratified by sex and age, further adjusted for patient characteristics, was used to determine the association of HF with exacerbation risk. MAIN RESULTS: 86 795 patients with COPD were categorised as no evidence of HF (n=60 047), possible HF (n=8476) and newly diagnosed HF (n=2066). Newly diagnosed HF (adjusted HR (aHR): 1.45, 95% CI: 1.30 to 1.62) and possible HF (aHR: 1.65, 95% CI: 1.58 to 1.72) similarly increased exacerbation risk. Incident and prevalent use of all HF medications were associated with increased exacerbation risk. Prevalent use was associated with reduced exacerbation risk compared with incident use. CONCLUSIONS: Earlier opportunities to improve the diagnosis and management of HF in the COPD population are missed. Managing HF may reduce exacerbation risk in the long term.

Hospitalisation and mortality in patients with comorbid COPD and heart failure: a systematic review and meta-analysis.

BACKGROUND: Discrepancy exists amongst studies investigating the effect of comorbid heart failure (HF) on the morbidity and mortality of chronic obstructive pulmonary disease (COPD) patients. METHODS: MEDLINE and Embase were searched using a pre-specified search strategy for studies comparing hospitalisation, rehospitalisation, and mortality of COPD patients with and without HF. Studies must have reported crude and/or adjusted rate ratios, risk ratios, odds ratios (OR), or hazard ratios (HR). RESULTS: Twenty-eight publications, reporting 55 effect estimates, were identified that compared COPD patients with HF with those without HF. One study reported on all-cause hospitalisation (1 rate ratio). Two studies reported on COPD-related hospitalisation (1 rate ratio, 2 OR). One study reported on COPD- or cardiovascular-related hospitalisation (4 HR). One study reported on 90-day all-cause rehospitalisation (1 risk ratio). One study reported on 3-year all-cause rehospitalisation (2 HR). Four studies reported on 30-day COPD-related rehospitalisation (1 risk ratio; 5 OR). Two studies reported on 1-year COPD-related rehospitalisation (1 risk ratio; 1 HR). One study reported on 3-year COPD-related rehospitalisation (2 HR). Eighteen studies reported on all-cause mortality (1 risk ratio; 4 OR; 24 HR). Five studies reported on all-cause inpatient mortality (1 risk ratio; 4 OR). Meta-analyses of hospitalisation and rehospitalisation were not possible due to insufficient data for all individual effect measures. Meta-analysis of studies requiring spirometry for the diagnosis of COPD found that risk of all-cause mortality was 1.61 (pooled HR; 95%CI: 1.38, 1.83) higher in patients with HF than in those without HF. CONCLUSIONS: In this systematic review, we investigated the effect of HF comorbidity on hospitalisation and mortality of COPD patients. There is substantial evidence that HF comorbidity increases COPD-related rehospitalisation and all-cause mortality of COPD patients. The effect of HF comorbidity may differ depending on COPD phenotype, HF type, or HF severity and should be the topic of future research.

Changing causes of death for patients with chronic respiratory disease in England, 2005-2015.

BACKGROUND: Chronic respiratory diseases (CRD) are common, are increasing in prevalence, and cause significant morbidity and mortality worldwide. However, we have limited knowledge on causes of death of patients with CRD in the general population. OBJECTIVE: We evaluated mortality rates and causes of death over time in patients with CRD. METHODS: We used linked primary care and mortality data to determine mortality rates and the most common causes of death in people with CRD (including asthma, bronchiectasis, COPD and interstitial lung diseases (ILD)) during 2005-2015 in England. RESULTS: We identified 558 888 patients with CRD (451 830 asthma, 137 709 COPD, 19 374 bronchiectasis, 10 745 ILD). The age-standardised mortality rate of patients with CRD was 1607 per 100 000 persons (asthma=856, COPD=1503, ILD=2609, bronchiectasis=1463). CRD mortality was overall 54% higher than the general population. A third of patients with CRD died from respiratory-related causes. Respiratory-related mortality was constant, while cardiovascular-related mortality decreased significantly over time. COPD accounted for the majority of respiratory-related deaths (66% overall) in all patient groups except ILD. CONCLUSIONS: Patients with CRD continue to experience substantial morbidity and mortality due to respiratory diseases. Disease-modifying intervention strategies are needed to improve outcomes for patients with CRD.

Risk factors and secondary care utilisation in a primary care population with non-tuberculous mycobacterial disease in the UK.

Prior research has identified risk factors associated with developing non-tuberculous mycobacterial disease (NTMD); we identified risk factors and secondary care utilisation of NTMD patients in the UK. This was a matched case-control study using electronic healthcare records from Clinical Practice Research Datalink from 2006 to 2016. NTMD was defined using prescription data and Read codes, based on international guidelines. Risk factors for NTMD were investigated using conditional logistic regression within a representative general population. All-cause secondary care utilisation (combined inpatient, outpatient, emergency visits) was investigated for participants with linked Hospital Episode Statistics (HES), using incidence rate ratio (IRR) from 2007 to 2015. We identified 1225 individuals with NTMD. A subset of individuals (426 patients) were eligible for linkage with HES. In the adjusted model, risk factors most strongly associated with an increased likelihood of NTMD included previous tuberculosis (OR 69.0; 47.7-99.8); bronchiectasis (OR 23.3; 12.4-43.9); lung cancer (OR 14.9; 3.98-55.7); oral corticosteroids (OCS; OR 7.28; 4.94-10.7); immunosuppressive (excluding corticosteroids) medication (OR 3.05; 1.15-8.10); being underweight (odds ratio (OR) 2.92; 95% CI 1.95, 4.36); and rheumatoid arthritis (OR 2.12; 1.05-4.27). NTMD patients had significantly higher rates of all-cause secondary care utilisation than non-NTMD patients (IRR 5.80; 5.14-6.46). Using a representative adult population, we identified prior TB, bronchiectasis, lung cancer, immunosuppressive medication, and OCS as the risk factors associated with the highest odds of developing NTMD in the UK. Patients with NTMD experienced nearly six times more all-cause secondary care events following their NTMD diagnosis than patients without NTMD.

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.

Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

OBJECTIVES: To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses. METHODS: Systematic searches MEDLINE and Embase based on predetermined criteria. Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: <20 weeks), lung function (≥12 weeks), health-related quality of life, mortality and adverse events. Qualitative comparisons of efficacies between RCTs and observational studies. RESULTS: 212 RCTs and 19 observational studies were included. Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)). No differences in lung function (0.02 (95% CI: -0.10 to 0.14)), health-related quality of life (-1.12 (95% CI: -3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found. Most of the observational evidence trended in the same direction as pooled RCT data. CONCLUSION: Further evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits. PROSPERO REGISTRATION NUMBER: CRD42018088013.

Temporal Trends in the Incidence of Heart Failure among Patients with Chronic Obstructive Pulmonary Disease and Its Association with Mortality.

Rationale: Heart failure (HF) is a common comorbidity in the chronic obstructive pulmonary disease (COPD) population, but previous research has shown underrecognition.Objectives: The objectives of this study were to determine the incidence of HF in a prevalent COPD cohort and 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-naive primary care COPD population was calculated for each year from 2006 to 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 >35 years old at COPD diagnosis, have a history of smoking, and have documented airflow obstruction. The Office of National Statistics provided mortality data for England. Adjusted mortality rate ratios (aMRRs) 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, body mass index, severity of airflow limitation, smoking status, history of cardiovascular disease, and diabetes.Results: We identified 95,987 HF-naive patients with COPD. Crude incidence of HF was steady from 2006 to 2016 (1.18 per 100 person-years; 95% confidence interval [CI], 1.09-1.27). Patients with COPD-iHF experienced greater than threefold increase in 1-year mortality and twofold increase in 5-year and 10-year mortality compared with patients with COPD-no HF, with no change on the basis of year of HF diagnosis. Mortality of patients with COPD-iHF did not improve over time, comparing incident HF in 2011 (1-yr aMRR, 1.26; 95% CI, 0.83-1.90; 5-yr aMRR, 1.26; 95% CI, 0.98-1.61) and 2015 (1-yr 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.

Protocol for a systematic literature review and network meta-analysis of the clinical benefit of inhaled maintenance therapies in chronic obstructive pulmonary disease.

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. PROSPERO REGISTRATION NUMBER: CRD42018088013.

European Respiratory Society International Congress 2018: four shades of epidemiology and tobacco control.

In this article, early career members and experienced members of the Epidemiology and Environment Assembly of the European Respiratory Society highlight and summarise a selection of six sessions from the Society's annual congress, which in 2018 was held in Paris, France. The topics covered in these sessions span from cutting-edge molecular epidemiology of lung function to clinical, occupational and environmental epidemiology of respiratory disease, and from emergent tobacco products to tobacco control.

Hospitalisation and mortality outcomes of patients with comorbid COPD and heart failure: a systematic review protocol.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often coexist in patients. Many studies have explored the short-term and long-term outcomes of patients with comorbid COPD and HF; however, there have been discrepancies in their findings. METHODS AND ANALYSIS: In this systematic review, MEDLINE and Embase will be searched using a prespecified search strategy. Randomised controlled trials and studies conducted in the general population that employ analytical or descriptive (longitudinal or case-control) study designs that report odds ratios (ORs), hazard ratios (HRs), or risk ratios (RRs) of mortality or hospitalisation, comparing patients with comorbid COPD and HF with patients with just COPD, will be selected. Screening by title and abstract, then full-text screening will be conducted by two reviewers. The Population, Exposure, Comparator, Outcomes, Study (PECOS) characteristics framework will be used to systemise the data extraction from selected studies. Study quality will be assessed using an adapted version of the Newcastle-Ottawa risk of bias tool. Data extraction and the risk of bias will also be conducted by two reviewers. Given sufficient homogeneity of selected studies, a meta-analysis will be conducted. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria will be used to assess the quality of cumulative evidence. DISSEMINATION: With this review, we hope to improve the understanding of clinical outcomes of patients with comorbid COPD and HF. We intend to publish the results of our review in a peer-reviewed journal and to present our findings at national and international meetings and conferences. PROSPERO REGISTRATION NUMBER: CRD42018089534.