Publications
39 results found
Whittaker H, Kallis C, Bolton T, et al., 2024, Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease, International Journal of Epidemiology, ISSN: 0300-5771
Whittaker H, Torkpour A, Quint J, 2024, Eligibility of patients with chronic obstructive pulmonary disease for inclusion in randomised control trials investigating triple therapy: A study using routinely collected data, Respiratory Research, Vol: 25, ISSN: 1465-9921
Background:Randomised control trials (RCTs) with strict eligibility criteria can lead to trial populations not commonly seen in clinical practice. We described the proportion of people with chronic obstructive pulmonary disease (COPD) in England eligible for RCTs investigating treatment with triple therapy.Methods:MEDLINE and Clinicaltrials.gov were searched for RCTs investigating triple therapy and eligibility criteria for each trial were extracted. Using routinely collected primary care data from Clinical Practice Research Datalink Aurum linked with Hospital Episode Statistics, we defined a population of COPD patients registered at a general practice in England, who were ≥ 40 years old, and had a history of smoking. Inclusion date was January 1, 2020. Patients who died earlier or left the general practice were excluded. Eligibility criteria for each RCT was applied to the population of COPD patients and the proportion of patients meeting each trial eligibility criteria were described.Results:26 RCTs investigating triple therapy were identified from the literature. The most common eligibility criteria were post-bronchodilator FEV1% predicted 30–80%, ≥ 2 moderate/≥ 1 severe exacerbations 12-months prior, no moderate exacerbations one-month prior and no severe exacerbations three-months prior, and the use of maintenance therapy or ICS use prior to inclusion. After applying each RCT eligibility criteria to our population of 79,810 COPD patients, a median of 11.2% [interquartile range (IQR) 1.8–17.4] of patients met eligibility criteria. The most discriminatory criteria included the presence exacerbations of COPD and previous COPD related medication use with a median of 67.6% (IQR 8.5–73.4) and 63% (IQR 69.3–38.4) of COPD patients not meeting these criteria, respectively.Conclusion:Data from these RCTs may not be generalisable to the wider population of people with COPD seen in everyday clinical practice and real-wo
Graul E, Nordon C, Rhodes K, et al., 2023, Temporal risk of nonfatal cardiovascular events post chronic obstructive pulmonary disease exacerbation, American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X
Rationale: Cardiovascular events following COPD exacerbations are recognised. Studies to date have been post-hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally. Objectives: We explore temporal relationships between moderate and severe exacerbations with incident, non-fatal hospitalised cardiovascular events, in a primary care-derived COPD cohort. Methods: We included people with COPD in England from 2014-2020, using Clinical Practice Research Datalink(CPRD) Aurum primary care database. Index date was first COPD exacerbation, or for those without exacerbation, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischaemic stroke, pulmonary hypertension) from linked hospital data. Adjusted Cox Regression models estimated average and time-stratified hazard ratios(aHR). Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation;119,124 (55.8%) moderate exacerbation and 27,324 (12.8%) a severe exacerbation. 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate post any exacerbation (1-14 days,aHR=3.19,95%CI 2.71-3.76), followed by progressively declining yet maintained effects, elevated after one year(aHR=1.84,1.78-1.91). HRs were highest 1-14 days following severe exacerbations (aHR=14.5,12.2-17.3) but highest 14-30 days following moderate exacerbations (aHR=1.94,1.63-2.31). Cardiovascular outcomes with greatest two-week effects post severe exacerbation were arrhythmia (aHR=12.7,10.3-15.7) and heart failure (aHR=8.31,6.79-10.2). Conclusions: Cardiovascular events following moderate exacerbations occur slightly later than severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately following exacerbation presents a cr
Graul E, Nordon C, Rhodes K, et al., 2023, Temporal risk of non-fatal cardiovascular events post COPD exacerbation: a population-based study, American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X
Rationale: Cardiovascular events following COPD exacerbations are recognised. Studies to date have been post-hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally. Objectives: We explore temporal relationships between moderate and severe exacerbations with incident, non-fatal hospitalised cardiovascular events, in a primary care-derived COPD cohort. Methods: We included people with COPD in England from 2014-2020, using Clinical Practice Research Datalink(CPRD) Aurum primary care database. Index date was first COPD exacerbation, or for those without exacerbation, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischaemic stroke, pulmonary hypertension) from linked hospital data. Adjusted Cox Regression models estimated average and time-stratified hazard ratios(aHR). Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation;119,124 (55.8%) moderate exacerbation and 27,324 (12.8%) a severe exacerbation. 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate post any exacerbation (1-14 days,aHR=3.19,95%CI 2.71-3.76), followed by progressively declining yet maintained effects, elevated after one year(aHR=1.84,1.78-1.91). HRs were highest 1-14 days following severe exacerbations (aHR=14.5,12.2-17.3) but highest 14-30 days following moderate exacerbations (aHR=1.94,1.63-2.31). Cardiovascular outcomes with greatest two-week effects post severe exacerbation were arrhythmia (aHR=12.7,10.3-15.7) and heart failure (aHR=8.31,6.79-10.2). Conclusions: Cardiovascular events following moderate exacerbations occur slightly later than severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately following exacerbation presents a cr
Whittaker H, Rothnie K, Quint J, 2023, Exploring the impact of varying definitions of exacerbations of chronic obstructive pulmonary disease in routinely collected electronic medical records, PLoS One, Vol: 18, ISSN: 1932-6203
Background:Validity of exposure and outcome measures in electronic medical records is vital to ensure robust, comparable study findings however, despite validation studies, definitions of variables used often differ. Using exacerbations of chronic obstructive pulmonary disease (COPD) as an example, we investigated the impact of potential misclassification of different definitions commonly used in publications on study findings.Methods:A retrospective cohort study was performed. English primary care data from the Clinical Practice Research Datalink Aurum database with linked secondary care data were used to define a population of COPD patients ≥40 years old registered at a general practice. Index date was the date eligibility criteria were met and end of follow-up was 30/12/19, death or end of data collection. Exacerbations were defined using 6 algorithms based on definitions commonly used in the literature, including one validated definition. For each algorithm, the proportion of frequent exacerbators (≥2 exacerbations/year) and exacerbation rates were described. Cox proportional hazard regression was used to investigate each algorithm on the association between heart failure and risk of COPD exacerbation.Findings:A total of 315,184 patients were included. Baseline proportion of frequent exacerbators varied from 2.7% to 15.3% depending on the algorithm. Rates of exacerbations over follow-up varied from 19.3 to 66.6 events/100 person-years. The adjusted hazard ratio for the association between heart failure and exacerbation varied from 1.45, 95% confidence intervals 1.42–1.49, to 1.01, 0.98–1.04.Interpretation:The use of high validity definitions and standardisation of definitions in electronic medical records is crucial to generating high quality, robust evidence.
Lenoir A, Whittaker H, Gayle A, et al., 2023, Mortality in non-exacerbating COPD: a longitudinal analysis of UK primary care data, Thorax, Vol: 78, Pages: 904-911, ISSN: 0040-6376
Introduction: Non-exacerbating patients with chronic obstructive pulmonary disease (COPD) are a less studied phenotype. We investigated clinical characteristics, mortality rates and causes of death among non-exacerbating compared with exacerbating patients with COPD.Methods: We used data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics between 1 January 2004 and 31 December 2018. Ever smokers with a COPD diagnosis with minimum 3 years of baseline information were included. We compared overall using Cox regression and cause-specific mortality rates using competing risk analysis, adjusted for age, sex, deprivation, smoking status, body mass index, GOLD stage and comorbidities. Causes of death were identified using International Classification of Diseases-10 codes.Results: Among 67 516 patients, 17.3% did not exacerbate during the 3-year baseline period. Mean follow-up was 4 years. Non-exacerbators were more likely to be male (63.3% vs 52.4%, p<0.001) and less often had a history of asthma (33.9% vs 43.6%, p<0.001) or FEV1<50% predicted (23.7 vs 31.8%) compared with exacerbators. Adjusted HR for overall mortality in non-exacerbators compared with exacerbators was 0.62 (95% CI 0.56 to 0.70) in the first year of follow-up and 0.87 (95% CI 0.83 to 0.91) thereafter. Non-exacerbating patients with COPD died less of respiratory causes than exacerbators (29.2% vs 40.3%) and more of malignancies (29.4% vs 23.4%) and cardiovascular diseases (26.2% vs 22.9%). HRs for malignant and circulatory causes of death were increased after the first year of follow-up.Discussion: In this primary care cohort, non-exacerbators showed distinct clinical characteristics and lower mortality rates. Non-exacerbators were equally likely to die of respiratory, malignant or cardiovascular diseases.
Whittaker H, Nordon C, Rubino A, et al., 2023, Frequency and severity of respiratory infections prior to COPD diagnosis and risk of subsequent post-diagnosis COPD exacerbations and mortality: EXACOS-UK health care data study, Thorax, Vol: 78, Pages: 760-766, ISSN: 0040-6376
ObjectiveLittle is known about how lower respiratory tract infections (LRTIs) before chronic obstructive pulmonary disease (COPD) are associated with future exacerbations and mortality. We investigated this association in COPD patients in England. MethodsClinical Practice Research Datalink Aurum, Hospital Episode Statistics, and Office of National Statistics data were used. Start of follow-up was patient’s first ever COPD diagnosis date and a 1-year baseline period prior to start of follow-up was used to find mild LRTIs (GP events/no antibiotics), moderate LRTIs (GP events +antibiotics), and severe LRTIs (hospitalised). Patients were categorised as having: none, 1 mild only, 2+ mild only, 1 moderate, 2+ moderate, and 1+ severe. Negative binomial regression modelled the association between baseline LRTIs and subsequent COPD exacerbations and Cox regression was used to investigate mortality. ResultsIn 215,234 COPD patients, increasing frequency and severity of mild and moderate LRTIs were associated with increased rates of subsequent exacerbations compared to no recorded LRTIs (1 mild adjusted IRR 1.16, 95%CI 1.14-1.18, 2+ mild IRR 1.51, 95%CI 1.46-1.55, 1 moderate IRR 1.81, 95%CI 1.78-1.85, 2+ moderate IRR 2.55, 95%CI 2.48-2.63). Patients with 1+ severe LRTI (vs. no baseline LRTIs) also showed an increased rate of future exacerbations (adjusted IRR 1.75, 95%CI, 1.70-1.80). This pattern of association was similar for risk of all-cause and COPD-related mortality however, patients with 1+ severe LRTIs had the highest risk of all-cause and COPD mortality. ConclusionIncreasing frequency and severity of LRTIs prior to COPD diagnosis were associated with increasing rates of subsequent exacerbations, and increasing risk all-cause and COPD-related mortality.
Zhang X, Quint JK, Whittaker H, 2023, Inequalities in respiratory health based on sex and gender, ERS Monograph, Vol: 2023, Pages: 40-50, ISSN: 2312-508X
There is a growing body of literature showing that sex and gender affect the incidence, susceptibility, presentation, diagnosis and severity of lung diseases. However, despite the availability of data on differences in health outcomes, current medical practice does not take sex and gender sufficiently into account in relation to disease management. In this chapter, we explore the importance of considering sex and gender relative to outcomes in chronic respiratory diseases to promote disease prevention and better management for respiratory patients.
Gadhvi K, Kandeil M, Raveendran D, et al., 2023, Inhaled corticosteroids and risk of cardiovascular disease in chronic obstructive pulmonary disease: a systematic review and meta-regression, Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, Vol: 10, Pages: 317-327, ISSN: 2372-952X
Background: Previous studies have reported mixed associations between inhaled corticosteroids (ICSs) and cardiovascular disease(CVD) in people with chronic obstructive pulmonary disease (COPD). Using updated literature, we investigated the associationbetween ICS-containing medications and CVD in COPD patients, stratified by study-related factors.Methods: We searched MEDLINE and EMBASE for studies that reported effect estimates for the association between ICS-containingmedications and the risk of CVD in COPD patients. CVD outcomes specifically included heart failure, myocardial infarction, andstroke-related events. We conducted a random-effects meta-analysis and a meta-regression to identify effect-modifying study-relatedfactors.Results: Fifteen studies met inclusion criteria and investigated the association between ICS-containing medications and the risk ofCVD. Pooled results from our meta-analysis showed a significant association between ICS-containing medication and reduced risk ofCVD (hazard ratio 0.87, 95% confidence intervals 0.78 to 0.97). Study follow-up time, non-ICS comparator, and exclusion of patientswith previous CVD modified the association between ICS use and risk of CVD.Conclusions: Overall, we found an association between ICS-containing medications and reduced risk of CVD in COPD patients.Results from the meta-regression suggest that subgroups of COPD patients may benefit from ICS use more than others and furtherwork is needed to determine this.
Whittaker HR, Wing K, Douglas I, et al., 2022, Inhaled corticosteroid withdrawal and change in lung function in primary care chronic obstructive pulmonary disease patients in England, Annals of the American Thoracic Society, Vol: 19, Pages: 1834-1841, ISSN: 1546-3222
RATIONALE: In COPD, inhaled corticosteroids (ICS) are associated with pneumonia highlighting the importance of investigating subgroups of patients who may benefit from prolonged ICS use. Despite this, the WISDOM trial found a greater decline in forced expiratory volume in 1 second (FEV1) in COPD patients who withdrew from inhaled corticosteroids (ICS) compared to patients who remained on triple therapy (TT). OBJECTIVES: We investigated the association between ICS withdrawal and rate of FEV1 decline in COPD patients using routinely collected electronic healthcare records. METHODS: Using Clinical Practice Research Datalink (CPRD) Aurum and Hospital episode statistics we included COPD patients who had been on TT for at least four months. Patients were categorised into those who withdrew from ICS and those who remained on TT during follow-up. Three cohorts were created: i) patients meeting the WISDOM trial eligibility criteria; ii) patients with COPD not restricted by the WISDOM trial eligibility criteria; and iii) patients who would have been excluded from the WISDOM trial based on their comorbidities. Mixed linear regression was used to model the association between ICS withdrawal and rate of FEV1 decline (ml/year) adjusted for baseline characteristics. RESULTS: 6,008 COPD patients met the WISDOM eligibility criteria, of which 9.0% withdrew from ICS. Mean rates of FEV1 decline -7.8 ml/year (95% CI -19.7 to +4.1) for withdrawers and -15.2 ml/year (95% CI -18.7 to -11.8) for those who remained on TT (difference p=0.264). 60,645 COPD patients were not restricted by the WISDOM eligibility criteria. Mean rate of FEV1 decline was -32.6ml/year (-33.6 to -31.5) for withdrawers and -36.4ml/year (-39.4 to -33.4) for those who remained on TT. 32,882 COPD patients were included in the last population representing those would have been excluded from the WISDOM trial due to their comorbidities. Mean rate of FEV1 decline was -29.4ml/year in withdrawers and -31.3ml/year in those who
Whittaker H, Van Ganse E, Dalon F, et al., 2022, Differences in severe exacerbations rates and health care utilisation in COPD populations in the UK and France, BMJ Open, Vol: 9, ISSN: 2044-6055
IntroductionChronic obstructive pulmonary disease (COPD) is a leading cause of mortality in Europe; however, it is important to understand how clinical practice patterns differ between countries and how this might relate to disease outcomes, to identify ways of improving local disease management. We aimed to describe and compare the management of COPD patients in the UK and France between 2008 and 2017. MethodsWe used data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics in the UK and the Echantillon Généraliste des Bénéficiaire in France to identify COPD patients each year between 2008 and 2017. We compared patient characteristics, all-cause mortality, and COPD exacerbations each year between 2008 and 2017 for patients in the UK and France separately. Health care utilisation and COPD exacerbations in 2017 were compared between France and the UK using t-tests and chi-squared tests. ResultsCOPD patients were similar in gender and comorbidities in both countries. In the UK, incidence of COPD exacerbations remained stable in the UK and France between 2007-2017. In 2017, the proportion of all-cause and COPD-related hospitalisations was greater in the UK than in France (43.9% vs. 32.8% and 8.3% vs 4.9%, respectively; p<0.001) as was the proportion of patients visiting accident and emergency (39.8% vs 16.2%, respectively; p<0.001). In addition, the mean length of stay in hospital for COPD related causes was shorted in the UK than in France (6.2 days (SD 8.4) vs 10.5 days (SD 9.1), respectively; p<0.001). DiscussionOverall, UK patients were more likely to go to accident and emergency (A&E) and be hospitalised for COPD-related causes and stay in hospital for fewer days after being admitted for COPD-related reasons compared to patients in France, illustrating a difference in health-seeking behaviours and access to healthcare.
Koteci A, Morgan A, Portas L, et al., 2022, Left-sided heart failure burden and mortality in idiopathic pulmonary fibrosis: a population-based study, BMC Pulmonary Medicine, Vol: 22, Pages: 1-11, ISSN: 1471-2466
BackgroundCardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data.MethodsClinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression.ResultsFrom 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2–34.6) in 2010 to 20.9% (20.0–21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9–4.8) in 2017 to 3.4 (3.0–3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03–1.14) for all-cause mortality; 1.32 (1.09–1.59) for cardiovascular mortality).ConclusionLeft-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors.
Whittaker H, Rothnie KJ, Quint JK, 2022, Causes of Mortality by GOLD Grade Airflow Obstruction in People with Chronic Obstructive Pulmonary Disease in England, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Whittaker H, Rubino A, Mullerova H, et al., 2022, Frequency and severity of exacerbations of COPD associated with future Risk of exacerbations and mortality: A UK routine health care data study, The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 17, Pages: 427-437, ISSN: 1176-9106
Background: Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes.Objective: To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort.Methods: Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up.Results: Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66– 1.74), 2.31 (95% CI 2.24– 2.37), and 3.52 (95% CI 3.43– 3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion.Conclusion: Increasing number and severity o
MacRae C, Whittaker H, Mukherjee M, et al., 2022, Deriving a standardised recommended respiratory disease codelist repository for future research, Pragmatic and Observational Research, Vol: 13, ISSN: 1179-7266
Background: Electronic health record (EHR) databases provide rich, longitudinal data on interactions with healthcare providers, and can be used to advance research into respiratory conditions. However, since these data are primarily collected to support health care delivery, clinical coding can be inconsistent, resulting in inherent challenges in using these data for research purposes.Methods: We systematically searched existing international literature and UK code repositories to find respiratory disease codelists for asthma from January 2018, and chronic obstructive pulmonary disease 1 and respiratory tract infections from January 2020, based on prior searches. Medline searches using key terms provided article lists. Full-text articles, supplementary files, and reference lists were examined for codelists, and codelists repositories were searched. A reproducible methodology for codelists creation was developed with recommended lists for each disease created based on multidisciplinary expert opinion and previously published literature. Results: Medline searches returned 1,126 asthma articles, 70 COPD articles, and 90 respiratory infection articles, with 3%, 22% and 5% including codelists, respectively. Repository searching returned 12 asthma, 23 COPD, and 64 respiratory infection codelists. We have systematically compiled respiratory disease codelists and from these derived recommended lists for use by researchers to find the most up-to-date and relevant respiratory disease codelists that can be tailored to individual research questions. Conclusions: Few published papers include codelists, and where published diverse codelists were used, even when answering similar research questions. Whilst some advances have been made. greater consistency and transparency across studies using routine data to study respiratory diseases are needed.
Whittaker H, Gulea C, Koteci A, et al., 2021, GP consultation rates for post-acute COVID-19 sequelae in cases managed in the community or hospital in the UK: a population-based study, BMJ: British Medical Journal, Vol: 375, Pages: 1-13, ISSN: 0959-535X
ObjectiveTo 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. DesignPopulation-based cohort study.Setting1,392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.Participants456,002 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 measuresComparison 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<0.001), venous thromboembolism (VTE) (3.35 [2.87 to 3.90]; p<0.001), lung fibrosis (2.41 [1.37 to 4.25]; p=0.002), and muscle pain (1.89 [1.6 3to 2.20]; p<0.001), as well as HCU post COVID-19 diagnosis compared with 1-year prior. In terms of absolute proportions, the most common outcomes ≥ 4-weeks post-CO
Koteci A, Morgan AD, Whittaker HR, et al., 2021, INCIDENCE AND PREVALENCE OF LEFT-SIDED HEART FAILURE IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS: A POPULATION-BASED STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A148-A149, ISSN: 0040-6376
Whittaker H, Kiddle S, Douglas I, et al., 2021, ICS withdrawal and rate of FEV1 decline in a primary care COPD population in England, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Lenoir A, Whittaker HR, Gayle A, et al., 2021, Clinical characteristics, mortality rates and causes of death in non-exacerbating COPD patients. A longitudinal cohort analysis of UK primary care data, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Whittaker H, Rubino A, Mullerova H, et al., 2021, Increasing risk of exacerbation and mortality associated with increasing frequency and severity of exacerbations in COPD patients: EXACOS-UK, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Whittaker H, Kiddle S, Quint J, 2021, Challenges and pitfalls of using repeat spirometry recordings in routine primary care data to measure FEV1 decline in a COPD population, Pragmatic and Observational Research, Vol: 2021, Pages: 119-130, ISSN: 1179-7266
BackgroundElectronic healthcare records (EHR) are increasingly used for epidemiological studies but are often viewed as lacking quality compared to randomised control trials and prospective cohorts. Studies of patients with chronic obstructive pulmonary disease (COPD) often use rate of forced expiratory volume in 1 second (FEV1) decline as an outcome however, its definition and robustness in EHR has not be investigated. We aimed to investigate how rate of FEV1 decline differs by the criteria used in an EHR database.MethodsClinical Practice Research Datalink and Hospital Episode Statistics were used. Patient populations were defined using 8 sets of criteria around repeated FEV1 measurements. At a minimum, patients had a diagnosis of COPD, were ≥35 years old, were current or ex-smokers, and had data recorded from 2004. FEV1 measurements recorded during follow-up were identified. Thereafter, eight populations were defined based on criteria around: i) the exclusion of patients or individual measurements with potential measurement error; ii) minimum number of FEV1 measurements; iii) minimum time interval between measurements; iv) specific timing of measurements; v) minimum follow-up time; and vi) the use of linked data. For each population, rate of FEV1 decline was estimated using mixed linear regression. ResultsFor 7/8 patient populations, rates of FEV1 decline (age and sex adjusted) were similar and ranged from -18.7ml/year (95%CI -19.2 to -18.2) to -16.5ml/year (95%CI -17.3 to -15.7). Rates of FEV1 decline in populations that excluded patients with potential measurement error ranged from -79.4ml/year (95%CI -80.7 to -78.2) to -46.8ml/year (95%CI -47.6 to -46.0). ConclusionsFEV1 decline remained similar in a COPD population regardless of number of FEV1 measurements, time intervals between measurements, follow-up period, exclusion of specific FEV1 measurements, and linkage to HES. However, exclusion of individuals with questionable data led to selection bias and fast
groves D, karsanji U, evans R, et al., 2021, Predicting future health risk in COPD: Differential impact of disease specific and multi-morbidity based risk stratification, International Journal of COPD, Vol: 2021, Pages: 1741-1754, ISSN: 1176-9106
Objective: Multi-morbidity contributes to mortality and hospitalisation in COPD but it is uncertain how this interacts with disease severity in risk prediction. We compared contributions of multi-morbidity and disease severity factors in modelling future health risk using UK primary care healthcare data. Method: Health records from 103,955 patients with COPD identified from the Clinical Practice Research Datalink were analysed. We compared Area Under The Curve (AUC) statistics for logistic regression (LR) models incorporating disease indices with models incorporating categorised co-morbidities. We also compared these models with performance of The John Hopkins Adjusted Clinical Groups® System (ACG) risk prediction algorithm. Results: LR models predicting all-cause mortality outperformed models predicting hospitalisation. Mortality was best predicted by disease severity (AUC & 95% CI: 0.816 (0.805 - 0.827)) and prediction was enhanced only marginally by the addition of multi-morbidity indices (AUC & 95% CI: 0.829 (0.818 – 0.839)). The model combining disease severity and multi-morbidity indices was a better predictor of hospitalisation (AUC & 95% CI: 0.679 (0.672 – 0.686)). ACG derived LR models outperformed conventional regression models for hospitalisation (AUC & 95% CI: 0.697 (0.690 – 0.704)) but not for mortality (AUC & 95% CI: 0.816 (0.805 – 0.827)). Conclusion: Stratification of future health risk in COPD can be undertaken using clinical and demographic data recorded in primary care but the impact of disease severity and multi-morbidity varies depending on the choice of health outcome. A more comprehensive risk modelling algorithm such as ACG offers enhanced prediction for hospitalisation by incorporating a wider range of coded diagnoses.
Whittaker HR, Gulea C, Koteci A, et al., 2021, Post-acute COVID-19 sequelae in cases managed in the community or hospital in the UK: a population based study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To compare post-COVID-19 sequelae between hospitalised and non-hospitalised individuals</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Population-based cohort study</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>1,383 general practices in England contributing to Clinical Practice Research Database Aurum</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>46,687 COVID-19 cases diagnosed between 1<jats:sup>st</jats:sup> August to 17<jats:sup>th</jats:sup> October 2020 (45.4% male; mean age 40), either hospitalised within two weeks of diagnosis or non-hospitalised, and followed-up for a maximum of three months.</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title><jats:p>Event rates of new symptoms, diseases, prescriptions and healthcare utilisation in hospitalised and non-hospitalised individuals, with between-group comparison using Cox regression. Outcomes compared at 6 and 12 months prior to index date, equating to first UK wave and pre-pandemic. Non-hospitalised group outcomes stratified by age and sex.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>45,272 of 46,687 people were non-hospitalised; 1,415 hospitalised. Hospitalised patients had higher rates of 13/26 symptoms and 11/19 diseases post-COVID-19 than the community group, received more prescriptions and utilised more healthcare. The largest differences were noted for rates per 100,000 person-weeks [95%CI] of <jats:italic>breathlessness:</jats:italic> 536 [432 to 663] v. 85 [77 to 93]; <jats:italic>joint pain:</jats:italic> 295 [221 to 392] v. 168 [158 to 179]
Whittaker H, Bloom C, Morgan A, et al., 2021, Accelerated FEV1 decline and risk of cardiovascular disease and mortality in a primary care population of COPD patients, European Respiratory Journal, Vol: 57, ISSN: 0903-1936
Accelerated lung function decline has been associated with increased risk of cardiovascular disease (CVD) in a general population, but little is known about this association in chronic obstructive pulmonary disease (COPD). We investigated the association between accelerated lung function decline and CVD outcomes and mortality in a primary care COPD population.COPD patients without a history of CVD were identified in the Clinical Practice Research Datalink (CPRD-GOLD) primary care dataset (n=36 282). Accelerated FEV1 decline was defined using the fastest quartile of the COPD population's decline. Cox regression assessed the association between baseline accelerated FEV1 decline and a composite CVD outcome over follow-up (myocardial infarction, ischaemic stroke, heart failure, atrial fibrillation, coronary artery disease, and CVD mortality). The model was adjusted for age, gender, smoking status, BMI, history of asthma, hypertension, diabetes, statin use, mMRC dyspnoea, exacerbation frequency, and baseline FEV1 percent predicted.6110 (16.8%) COPD patients had a CVD event during follow-up; median length of follow-up was 3.6 years [IQR 1.7–6.1]). Median rate of FEV1 decline was –19.4 mL·year−1 (IQR, –40.5 to 1.9); 9095 (25%) patients had accelerated FEV1 decline (>–40.5 mL·year−1), 27 287 (75%) did not (≤ –40.5 mL·year−1). Risk of CVD and mortality was similar between patients with and without accelerated FEV1 decline (HRadj 0.98 [95%CI, 0.90–1.06]). Corresponding risk estimates were 0.99 (95%CI 0.83–1.20) for heart failure, 0.89 (95%CI 0.70–1.12) for myocardial infarction, 1.01 (95%CI 0.82–1.23) for stroke, 0.97 (95%CI 0.81–1.15) for atrial fibrillation, 1.02 (95%CI 0.87–1.19) for coronary artery disease, and 0.94 (95%CI 0.71–1.25) for CVD mortality. Rather, risk of CVD was associated with mMRC score ≥2 and ≥2 exacerbations in the year prior.CVD out
Whittaker H, Pimenta J, Jarvis D, et al., 2020, Characteristics associated with accelerated lung function decline in a primary care population with chronic obstructive pulmonary disease, International Journal of COPD, Vol: 2020, Pages: 3079-3091, ISSN: 1176-9106
Background: Estimates for lung function decline in chronic obstructive pulmonary disease (COPD) have differed by study setting and have not been described in a UK primary care population.Purpose: To describe rates of FEV1 and FVC decline in COPD and investigate characteristics associated with accelerated decline.Patients and Methods: Current/ex-smoking COPD patients (35 years+) who had at least 2 FEV1 or FVC measurements ≥ 6 months apart were included using Clinical Practice Research Datalink. Patients were followed up for a maximum of 13 years. Accelerated rate of lung function decline was defined as the fastest quartile of decline using mixed linear regression, and association with baseline characteristics was investigated using logistic regression.Results: A total of 72,683 and 50,649 COPD patients had at least 2 FEV1 or FVC measurements, respectively. Median rates of FEV1 and FVC changes or decline were − 18.1mL/year (IQR: − 31.6 to − 6.0) and − 22.7mL/year (IQR: − 39.9 to − 6.7), respectively. Older age, high socioeconomic status, being underweight, high mMRC dyspnoea and frequent AECOPD or severe AECOPD were associated with an accelerated rate of FEV1 and FVC decline. Current smoking, mild airflow obstruction and inhaled corticosteroid treatment were additionally associated with accelerated FEV1 decline whilst women, sputum production and severe airflow obstruction were associated with accelerated FVC decline.Conclusion: Rate of FEV1 and FVC decline was similar and showed similar heterogeneity. Whilst FEV1 and FVC shared associations with baseline characteristics, a few differences highlighted the importance of both lung function measures in COPD progression. We identified important characteristics that should be monitored for disease progression.
Whittaker H, Quint JK, 2020, Using routine health data for research: the devil is in the detail, Thorax, Vol: 75, Pages: 714-715, ISSN: 0040-6376
Kiddle S, Whittaker H, Seaman S, et al., 2020, Prediction of five-year mortality after COPD diagnosis using primary care records, PLoS One, Vol: 15, ISSN: 1932-6203
Accurate prognosis information after a diagnosis of chronic obstructive pulmonary disease (COPD) would facilitate earlier and better informed decisions about the use of prevention strategies and advanced care plans. We therefore aimed to develop and validate an accurate prognosis model for incident COPD cases using only information present in general practitioner (GP) records at the point of diagnosis. Incident COPD patients between 2004–2012 over the age of 35 were studied using records from 396 general practices in England. We developed a model to predict all-cause five-year mortality at the point of COPD diagnosis, using 47,964 English patients. Our model uses age, gender, smoking status, body mass index, forced expiratory volume in 1-second (FEV1) % predicted and 16 co-morbidities (the same number as the Charlson Co-morbidity Index). The performance of our chosen model was validated in all countries of the UK (N = 48,304). Our model performed well, and performed consistently in validation data. The validation area under the curves in each country varied between 0.783–0.809 and the calibration slopes between 0.911–1.04. Our model performed better in this context than models based on the Charlson Co-morbidity Index or Cambridge Multimorbidity Score. We have developed and validated a model that outperforms general multimorbidity scores at predicting five-year mortality after COPD diagnosis. Our model includes only data routinely collected before COPD diagnosis, allowing it to be readily translated into clinical practice, and has been made available through an online risk calculator
Whittaker H, Connell O, Campbell J, et al., 2020, Eligibility for lung volume reduction surgery in chronic obstructive pulmonary disease patients identified in a UK primary care setting, Chest, Vol: 157, Pages: 276-285, ISSN: 0012-3692
BackgroundAlthough 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.MethodsClinical 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. ResultsAmong 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. ConclusionsA 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.
Bandosz P, Ahmadi-Abhari S, Guzman-Castillo M, et al., 2020, Potential impact of diabetes prevention on mortality and future burden of dementia and disability: a modelling study, DIABETOLOGIA, Vol: 63, Pages: 104-115, ISSN: 0012-186X
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Whittaker H, Morgan A, Jarvis D, et al., 2020, Accelerated Lung Function Decline and Rate of Cardiovascular Disease in a Primary Care Population of Chronic Obstructive Pulmonary Disease Patients in England, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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