Imperial College London

DrChloeBloom

Faculty of MedicineNational Heart & Lung Institute

Clinical Senior Lecturer in Respiratory Epidemiology
 
 
 
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Contact

 

chloe.bloom06

 
 
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Location

 

Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
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93 results found

Conway FM, Bloom CI, Shah PL, 2022, Susceptibility of patients with airways disease to SARS-CoV-2 infection., American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic. People with airways disease are at higher risk of respiratory infection, and viruses can trigger respiratory exacerbations. Patients with airways disease may therefore be more susceptible to SARS-CoV-2 infection, development of covid-19, or be at higher risk of adverse outcomes. Here we review susceptibility, based on current epidemiological studies, and explore biological mechanisms. Evidence from multiple large observational studies has shown chronic obstructive pulmonary disease (COPD) is a significant risk factor for covid-19 related mortality. Whether people with asthma are more susceptible to infection or severe outcomes has been much debated but appears to be related to their asthma phenotype and severity. To what extent these differences are biological or influenced by public health non-pharmacological interventions is difficult to quantify. Biological mechanisms that may influence susceptibility and adverse outcomes in airways disease include the increased expression of protein receptors enabling viral cell entry, dysfunctional epithelial airway immunity, type-2 inflammation and the use of inhaled corticosteroids. A better understanding of the susceptibility and mechanisms is essential for developing preventative and therapeutic strategies. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Journal article

Sundaram V, Nagai T, Chiang C-E, Reddy YN, Chao T-F, Zakeri R, Bloom C, Nakai M, Nishimura K, Hung C-L, Miyamoto Y, Yasuda S, Banerjee A, Anzai T, Simon D, Rajagopalan S, Cleland JGF, Sahadevan J, Quint JKet al., 2022, Hospitalization for Heart Failure in the United States, UK, Taiwan, and Japan: An International Comparison of Administrative Health Records on 413,385 Individual Patients, JOURNAL OF CARDIAC FAILURE, Vol: 28, Pages: 353-366, ISSN: 1071-9164

Journal article

Bloom C, Montonen J, Jons O, Garry EM, Bhatt SPet al., 2022, Treatment Transitions in Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases, PULMONARY THERAPY, Vol: 8, Pages: 75-93, ISSN: 2364-1754

Journal article

Bloom C, Montonen J, Jons O, Garry EM, Bhatt SPet al., 2022, First Maintenance Therapy for Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases, PULMONARY THERAPY, Vol: 8, Pages: 57-74, ISSN: 2364-1754

Journal article

Bloom C, Wong E, Hickman K, Elkin Set al., 2021, Influence of the first wave of COVID-19 on asthma inhaler prescriptions, npj Primary Care Respiratory Medicine, Vol: 31, ISSN: 2055-1010

In the beginning of the COVID-19 pandemic there were major concerns regarding the huge demand for asthma inhalers. Using primary care medical records for 614,700 asthma patients between January and June 2020, we found that there was a substantial increase in inhalers solely in March 2020. Patients significantly associated with receiving higher inhaled corticosteroid prescriptions were younger, of higher socioeconomic status and had milder asthma.

Journal article

Stewart I, Bloom C, 2021, Considerations for conducting and interpreting long-term follow-up of intervention studies: avoiding spoiled milk, THORAX, Vol: 76, Pages: 1067-1068, ISSN: 0040-6376

Journal article

Bloom CI, Johnston SL, 2021, Decline in respiratory and cardiac admissions during the COVID-19 pandemic: what is the role of common respiratory virus infections?, Respirology, Vol: 26, Pages: 1010-1011, ISSN: 1323-7799

Numerous countries across the globe have introduced a variety of public health measures, non-pharmaceutical interventions (NPIs), to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and accordingly reduce coronavirus disease 2019 (COVID-19) hospitalizations and mortality. Effective NPIs have at the same time caused considerable changes in healthcare demand for non-COVID-19 conditions. In New Zealand, during the first wave of the pandemic in early 2020, their government instigated a stringent programme of restrictions, with a four-level alert system, including border closure, quarantine for returning travellers, social distancing measures and personal hygiene promotion. High public compliance with NPIs prevented COVID-19 community transmission for 102 consecutive days. In fact, they were so effective that the usual winter influenza surge was also disrupted, with an extraordinary 99.9% reduction in influenza virus detections as compared to previous years and a substantial reduction in all other respiratory viruses, including a 98% reduction in respiratory syncytial virus detections.1 Due to the key role viruses are known to play in many respiratory conditions and are postulated to play in myocardial infarctions and heart failure, it may be hypothesized that the stringent reductions implemented in New Zealand may also have mitigated the incidence of these conditions during that time.

Journal article

Bloom CI, Cullinan P, Wedzicha JA, 2021, Asthma phenotypes and COVID-19 risk: a population-based observational study, American Journal of Respiratory and Critical Care Medicine, Vol: 205, Pages: 36-45, ISSN: 1073-449X

Rationale: Studies have suggested some asthma patients are at risk of severe COVID-19, but they have had limited data on asthma phenotype and have not considered if risks are specific to COVID-19. Objectives: Determine the effect of asthma phenotype on three levels of COVID-19 outcomes. Compare hospitalisation rates to influenza and pneumonia. Methods: Electronic medical records were used to identify asthma patients and match them to the general population. Patient-level data were linked to Public Health England SARS-CoV-2 test data, hospital, and mortality data. Asthma was phenotyped by medication, exacerbation history, and type-2 inflammation. The risk of each outcome, adjusted for major risk factors, was measured using Cox regression. Measurements and Main Results: 434,348 asthma and 748,327 matched patients were included. All asthma patients had a significantly increased risk of a GP-diagnosis of COVID-19. Asthma with regular inhaled corticosteroid (ICS) use (HR=1.27, 95%CI=1.01-1.61), intermittent ICS + add-on asthma medication use (HR=2.00, 95%CI=1.43-2.79), regular ICS + add-on use (HR=1.63, 95 CI=1.37-1.94), or with frequent exacerbations (HR=1.82, 95% CI=1.34-2.47) was significantly associated with hospitalisation. These phenotypes were significantly associated with influenza and pneumonia hospitalisations. Only patients with regular ICS + add-on asthma therapy (HR=1.70, 95%CI=1.27-2.26) or frequent exacerbations (HR=1.66, 95%CI=1.03-2.68) had a significantly higher risk of ICU admission or death. Atopy and blood eosinophil count were not associated with severe COVID-19 outcomes. Conclusions: More severe asthma was associated with more severe COVID-19 outcomes, but type-2 inflammation was not. The risk of COVID-19 hospitalisation appeared to be similar to the risk with influenza or pneumonia.

Journal article

Zakeri R, Morgan A, Sundaram V, Bloom C, Cleland J, Quint Jet al., 2021, Under-recognition of heart failure in patients with atrial fibrillation and the impact of gender: a UK population-based cohort study, BMC Medicine, Vol: 19, ISSN: 1741-7015

Background: Patients with atrial fibrillation (AF) complicated by heart failure (HF) have a poor prognosis. We investigated whether long-term loop-diuretic therapy in patients with AF and no known diagnosis of HF, as a potential surrogate marker of undiagnosed HF, is also associated with worse outcomes.Methods: Adults with incident AF were identified from UK primary and secondary care records between 2004-2016. Repeat prescriptions for loop-diuretics, without a diagnosis of HF or documented non-cardiac indication, were classified as ‘isolated’ loop-diuretic use.Results: Amongst 124,256 people with incident AF (median 76 years, 47% women), 22,001 (17.7%) had a diagnosis of HF, and 22,325 (18.0%) had isolated loop-diuretic use. During 2.9 (LQ-UQ 1-6) years’ follow-up, 12,182 patients were diagnosed with HF (incidence rate 3.2 [95%CI 3.1-3.3]/100 person-years). Of these, 3,999 (32.8%) had prior isolated loop-diuretic use, including 31% of patients diagnosed with HF following an emergency hospitalisation. The median time from AF to HF diagnosis was 3.6 (1.2-7.7) years in men versus 5.1 (1.8-9.9) years in women (p=0.0001). In adjusted models, patients with isolated loop-diuretic use had higher mortality (HR 1.42 [95%CI 1.37-1.47], p<0.0005) and risk of HF hospitalisation (HR 1.60 [95%CI 1.42-1.80], p<0.0005) than patients with no HF or loop-diuretic use, and comparably poor survival to patients with diagnosed HFConclusions: Loop-diuretics are commonly prescribed to patients with AF and may indicate increased cardiovascular risk. Targeted evaluation of these patients may allow earlier HF diagnosis, timely intervention and better outcomes, particularly amongst women with AF, in whom HF appears to be under-recognised and diagnosed later than in men.

Journal article

Altmann MC, Rinchai D, Baldwin N, Toufiq M, Whalen E, Garand M, Kabeer BSA, Alfaki M, Presnell S, Khaenam P, Benitez AA, Mougin F, Thébault P, Chiche L, Jourde-Chiche N, Phillips JT, Klintmalm G, O'Garra A, Berry M, Bloom C, Wilkinson RJ, Graham CM, Lipman M, Lertmemongkolchai G, Bedognetti D, Thiebaut R, Kheradmand F, Mejias A, Ramilo O, Palucka K, Pascual V, Banchereau J, Chaussabel Det al., 2021, Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data, Nature Communications, Vol: 12, Pages: 1-19, ISSN: 2041-1723

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via: https://drinchai.shinyapps.io/BloodGen3Module/.

Journal article

Bloom CI, Drake TM, Docherty AB, Lipworth BJ, Johnston SL, Nguyen-Van-Tam JS, Carson G, Dunning J, Harrison EM, Baillie JK, Semple MG, Cullinan P, Openshaw PJM, Alex B, Bach B, Barclay WS, Bogaert D, Chand M, Cooke GS, Filipe AD, Fletcher T, Green CA, Harrison EM, Hiscox JA, Ho AY, Horby PW, Ijaz S, Khoo S, Klenerman P, Law A, Lim WS, Mentzer AJ, Merson L, Meynert AM, Noursadeghi M, Moore SC, Palmarini M, Paxton WA, Pollakis G, Price N, Rambaut A, Robertson DL, Russell CD, Sancho-Shimizu V, Scott JT, Silva TD, Sigfrid L, Solomon T, Sriskandan S, Stuart D, Summers C, Tedder RS, Thomson EC, Thompson AAR, Thwaites RS, Turtle LCW, Zambon M, Hardwick H, Donohue C, Lyons R, Griffiths F, Oosthuyzen W, Norman L, Pius R, Fairfield CJ, Knight SR, Mclean KA, Murphy D, Shaw CA, Dalton J, Girvan M, Saviciute E, Roberts S, Harrison J, Marsh L, Connor M, Halpin S, Jackson C, Gamble C, Leeming G, Law A, Wham M, Clohisey S, Hendry R, Scott-Brown J, Greenhalf W, Shaw V, McDonald S, Keating S, Ahmed KA, Armstrong JA, Ashworth M, Asiimwe IG, Bakshi S, Barlow SL, Booth L, Brennan B, Bullock K, Catterall BWA, Clark JJ, Clarke EA, Cole S, Cooper L, Cox H, Davis C, Dincarslan O, Dunn C, Dyer P, Elliott A, Evans A, Finch L, Fisher LWS, Foster T, Garcia-Dorival I, Greenhalf W, Gunning P, Hartley C, Jensen RL, Jones CB, Jones TR, Khandaker S, King K, Kiy RT, Koukorava C, Lake A, Lant S, Latawiec D, Lavelle-Langham L, Lefteri D, Lett L, Livoti LA, Mancini M, McDonald S, McEvoy L, McLauchlan J, Metelmann S, Miah NS, Middleton J, Mitchell J, Moore SC, Murphy EG, Penrice-Randal R, Pilgrim J, Prince T, Reynolds W, Ridley PM, Sales D, Shaw VE, Shears RK, Small B, Subramaniam KS, Szemiel A, Taggart A, Tanianis-Hughes J, Thomas J, Trochu E, Tonder LV, Wilcock E, Zhang JE, Flaherty L, Maziere N, Cass E, Carracedo AD, Carlucci N, Holmes A, Massey H, Adeniji K, Agranoff D, Agwuh K, Ail D, Alegria A, Angus B, Ashish A, Atkinson D, Bari S, Barlow G, Barnass S, Barrett N, Bassford C, Baxter D, Beadsworth Met al., 2021, Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK, The Lancet Respiratory Medicine, Vol: 9, Pages: 699-711, ISSN: 2213-2600

BackgroundStudies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use.MethodsWe analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16–49 years, and ≥50 years). In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting β-agonists [SABAs], and long-acting β-agonists [LABAs]). Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma.Findings75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16–49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16–49 years: adjusted odds ratio [OR] 1·20 [95% CI

Journal article

Cook J, Bloom C, Lewis J, Marjenberg Z, Platz JH, Langham Set al., 2021, Impact of health technology assessment on prescribing patterns of inhaled fixed-dose combination triple therapy in chronic obstructive pulmonary disease., J Mark Access Health Policy, Vol: 9, Pages: 1-10, ISSN: 2001-6689

Background: Evidence suggests that triple therapy for patients with chronic obstructive pulmonary disease (COPD) is being used in a broader range of patients than recommended by guidelines, which may have health and cost implications. Objective: To explore the relationship between national health technology assessment (HTA) agency appraisals and market penetration of two fixed-dose combination (FDC) triple therapies. Study design: HTAs from Q3 2017 to Q1 2020 from 10 countries were evaluated. Intervention: Glycopyrronium bromide/formoterol fumarate/beclomethasone (Trimbow®) and umeclidinium/vilanterol/fluticasone furoate (Trelegy™ Ellipta®). Main outcome measure: HTA restrictions and prescribing rates (days of therapy). Results: Seven countries (70%) imposed restrictions on use including prescription only for patients stable on free-combination triple therapy or not controlled on dual therapy, requirement of a specialist prescription or therapeutic plan, prescription only for patients with severe COPD, and use as second-line therapy or later. In general, countries that have imposed restrictions on the use of FDC triple therapies have seen a lower than average uptake. Conclusion: Payer guidance on prescribing FDC triple therapy may potentially support more appropriate prescribing in line with clinical guidelines. It is important for payers to consider which restrictions would ensure the most efficient use of scarce resources.

Journal article

Bloom CI, Cullinan P, Wedzicha JA, 2021, Assessing Factors Associated with COVID19 Risk in Asthma, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Bloom C, Franklin C, Bush A, Saglani S, Quint Jet al., 2021, Burden of preschool wheeze and progression to asthma in the UK: population-based cohort 2007 to 2017, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 1949-1958, ISSN: 0091-6749

BackgroundWheeze is one of the most common symptoms of preschool children (age 1 to 5 years), yet we have little understanding of the burden in the UK.ObjectivesDetermine prevalence and pattern of physician-confirmed preschool wheeze, related healthcare utilisation, and factors associated with progression to school-age asthma.MethodsWe used nationally representative primary and secondary care electronic medical records between 2007-2017 to identify preschool children with wheeze. Factors associated with asthma progression were identified in a nested cohort of children with follow-up from 1-2 years of age, until at least 8 years of age.ResultsFrom 1,021,624 preschool children, 69,261 were identified with wheeze. Prevalence of preschool wheeze was 7.7% in 2017. Wheeze events were lowest in August and highest in late-autumn/early-winter. During median follow-up of 2.0 years (IQR 1.2-4.0), 15.8% attended an emergency department, and 13.9% had a hospital admission, for a respiratory disorder. The nested cohort with prolonged follow-up identified 15,085 children; 35.5% progressed to asthma between 5-8 years old. Of children with preschool wheeze, without an asthma diagnosis, 34.9% were prescribed inhaled corticosteroids, and 15.6% oral corticosteroids. The factors most strongly associated with progression to asthma were wheeze frequency and severity, atopy, prematurity, maternal asthma severity and first reported wheeze event occurring in September.ConclusionsPreschool wheeze causes considerable healthcare burden, a large number of children are prescribed asthma medication and have unplanned secondary care visits. Multiple factors influence progression to asthma, including first wheeze event occurring in September.

Journal article

Mallia P, Russell G, Meghji J, Wong B, Kumar K, Pilkington V, Chhabra S, Russell B, Chen J, Srikanthan K, Park M, Owles H, Liew F, Alcada J, Martin L, Coleman M, Elkin S, Ross C, Agrawal S, Gardiner T, Bell A, White A, Hampson D, Vithlani G, Manalan K, Bramer S, Martin S, Kucheria A, Ratnakumar P, Sheeka A, Anandan L, Copley S, Bloom C, Kon Oet al., 2021, Symptomatic, biochemical and radiographic recovery in patients with Covid-19, BMJ Open Respiratory Research, Vol: 8, ISSN: 2052-4439

Background: The symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described.Methods: Retrospective analysis of 401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness.Results: 75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge.Conclusions: Patients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19.

Journal article

Whittaker H, Bloom C, Morgan A, Jarvis D, Kiddle S, Quint Jet 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

Journal article

Naqvi SA, Patel R, Griffiths CJ, Bloom CIet al., 2021, P114 Systemic adverse effects from inhaled corticosteroid use in asthma: a systematic review, British Thoracic Society Winter Meeting, Publisher: BMJ Publishing Group, Pages: A151-A151, ISSN: 0040-6376

Background Oral corticosteroid (OCS) use increases the risk of systemic adverse effects including osteoporosis, fractures, diabetes, ocular disorders and respiratory infections. We sought to understand if there is an increased risk of these adverse effects from inhaled corticosteroids (ICS) use in adults with asthma.Methods MEDLINE and EMBASE databases were searched to identify studies measuring adverse effects with ICS use in asthma, with those investigating a majority population of COPD patients excluded. Studies were grouped by outcome: bone mineral density (BMD), respiratory infection (pneumonia, tuberculous or non-tuberculous mycobacterial infection), diabetes and ocular disorder (glaucoma or cataracts). Study information was extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomised controlled trials) and ROBINS-I tool (observational studies). A narrative synthesis was carried out due to the low number of studies with the same outcome measurement.Results Thirteen studies met the inclusion criteria, two trials and eleven observational studies, all analysing the effects of ICS compared with non-ICS use for particular outcomes. Study outcomes by number of studies were: six BMD, six infection (four pneumonia, one tuberculous, one non-tuberculous mycobacterial), one ocular disorder (cataracts) and no diabetes. Studies addressing BMD were limited by study size, lack of generalisability, and short follow-up. BMD was measured from a range of bones via ultrasound or x-ray absorptiometry; most found a loss of BMD. Studies addressing infection suffered from lack of power, misclassification and selection bias; most studies found an increased risk of infection. Only one study assessed ocular disorders, they found an increased risk of cataracts. This study likely suffered from residual confounding. Most studies were unable to fully account for OCS exposure, total ICS exposure or difference between ICS drugs and their varyi

Conference paper

Patel R, Naqvi S, Griffiths C, Bloom Cet al., 2020, Systemic adverse effects from inhaled corticosteroid use in asthma: a systematic review, BMJ Open Respiratory Research, Vol: 7, ISSN: 2052-4439

Background Oral corticosteroid use increases the risk of systemic adverse effects including osteoporosis, bone fractures, diabetes, ocular disorders and respiratory infections. We sought to understand if inhaled corticosteroid (ICS) use in asthma is also associated with increased risk of systemic effects.Methods MEDLINE and Embase databases were searched to identify studies that were designed to investigate ICS-related systemic adverse effects in people with asthma. Studies were grouped by outcome: bone mineral density (BMD), respiratory infection (pneumonia or mycobacterial infection), diabetes and ocular disorder (glaucoma or cataracts). Study information was extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomised controlled trials) and Risk of Bias In Non-randomised Studies of Interventions-I tool (observational studies). A narrative synthesis was carried out due to the low number of studies reporting each outcome.Results Thirteen studies met the inclusion criteria, 2 trials and 11 observational studies. Study numbers by outcome were: six BMD, six respiratory infections (four pneumonia, one tuberculosis (TB), one non-TB mycobacteria), one ocular disorder (cataracts) and no diabetes. BMD studies found conflicting results (three found loss of BMD and three found no loss), but were limited by study size, short follow-up and lack of generalisability. Studies addressing infection risk generally found positive associations but suffered from a lack of power, misclassification and selection bias. The one study which assessed ocular disorders found an increased risk of cataracts. Most studies were not able to fully adjust for known confounders, including oral corticosteroids.Conclusion There is a paucity of studies assessing systemic adverse effects associated with ICS use in asthma. Those studies that have been carried out present conflicting findings and are limited by multiple biases and residual confounding. Furth

Journal article

Bloom C, Ramsey H, Alter M, Lakhani S, Wong E, Hickman K, Elkin S, Majeed A, El-Osta Aet al., 2020, Qualitative study of practices and challenges of stepping down asthma medication in primary care across the UK, Journal of Asthma and Allergy, Vol: 13, Pages: 429-437, ISSN: 1178-6965

Background: Guidelines recommend that asthma treatment should be stepped down to the minimally effective dose that achieves symptom control to prevent medication side effects and reduce unnecessary costs. Little is known about the practice of stepping down and the challenges in primary care, where most asthma patients are managed.Objective: To explore views, experiences, barriers and ideas, of doctors, nurses and pharmacists working in primary care, related to step down of asthma medication.Methods: Primary care practitioners from across the UK participated in a survey and/or semi-structured interview. Questions explored four main areas: how asthma medication is reviewed, views on asthma guidelines, perceived barriers faced by healthcare workers and facilitators of stepping down. Qualitative content analysis enabled data coding of interview transcripts to identify major themes.Results: A total of 274 participants responded to the survey, 29 participated in an interview (12 doctors, 9 nurses, and 8 pharmacists), working in GP practices from across the UK. Nearly half of the survey participants infrequently step down asthma medication (doctors=42.7%, nurses=46.3%). Four major themes related to barriers to stepping down were (i) lack of awareness of the need to step down, (ii) inertia to step down, driven by low confidence in ability, fear of consequences, and concern for who is responsible for stepping down, (iii) self-efficacy of ability to step down, influenced by lack of clear, applied guidance and limited training, and (iv) feasibility of step down, driven by a lack of systematic acceptance of stepping down and time. Strategies proposed to reduce overtreatment included education and training, improved gathering of evidence and guidance, and integrating step down into routine asthma care.Conclusion: Failure to implement this guideline recommendation into everyday asthma management is influenced by several contributing factors. Future directions should include addre

Journal article

Bloom CI, Cabrera C, Arnetorp S, Coulton K, Nan C, van der Valk RJP, Quint JKet al., 2020, Asthma-related health outcomes associated with short-acting beta(2)-agonist inhaler use: an observational UK study as part of the SABINA global program, Advances in Therapy, Vol: 37, Pages: 4190-4208, ISSN: 0741-238X

IntroductionPatients with asthma typically increase short-acting β2-agonists (SABA) use with worsening symptoms. Excessive SABA use may lead to a higher risk of adverse outcomes. We evaluated, in a large population cohort, an association between SABA inhaler use and asthma exacerbations and healthcare utilization.MethodsAs part of the SABINA (SABA use IN Asthma) global program, we conducted a retrospective longitudinal observational study (SABINA I) using UK primary care electronic healthcare records (Clinical Practice Research Datalink; 2007–2017) from asthma patients aged ≥ 12 years. SABA inhaler use was classified as ‘high use ’ 3 canisters/year versus ‘low use’, 0–2 canisters/year. Taking into consideration all their asthma prescriptions, patients were categorized into a treatment step according to 2016 British Thoracic Society (BTS) asthma management guidelines. Multivariable regression assessed the association of SABA inhaler use by BTS treatment steps (grouped as BTS steps 1/2 and 3–5), separately, and with outcomes of exacerbations or asthma-related healthcare utilization (primary care and hospital outpatient consultations); only patients with linked hospital data were included in this analysis.ResultsOf the 574,913 patients included, 218,365 (38%) had high SABA inhaler use. Overall, 336,412 patients had linked hospital data. High SABA inhaler use was significantly associated with an increased risk of exacerbations [adjusted hazard ratio, 95% confidence interval (CI): BTS steps 1/2 = 1.20, 1.16–1.24; BTS steps 3–5 = 1.24, 1.20–1.28], asthma-related primary care consultations [adjusted incidence rate ratio (IRR), 95% CI: BTS steps 1/2 = 1.24, 1.23–1.26; BTS steps 3–5 = 1.13, 1.11–1.15), and asthma-related hospital outpatient consultations (adjusted IRR, 95% CI: BTS steps 1/2 = 1.19, 1.12&ndas

Journal article

Bloom C, de Preux L, Sheikh A, Quint Jet al., 2020, Health and cost impact of stepping down asthma medication for UK patients, 2001–2017: a population-based observational study, PLoS Medicine, Vol: 17, ISSN: 1549-1277

BackgroundGuidelines recommend stepping down asthma treatment to the minimum effective dose to achieve symptom control, prevent adverse side effects, and reduce costs. Limited data exist on asthma prescription patterns in a real-world setting. We aimed to evaluate the appropriateness of doses prescribed to a UK general asthma population and assess whether stepping down medication increased exacerbations or reliever use, as well as its impact on costs.Methods and findingsWe used nationwide UK primary care medical records, 2001–2017, to identify 508,459 adult asthma patients managed with preventer medication. Prescriptions of higher-level medication: medium/high-dose inhaled corticosteroids (ICSs) or ICSs + add-on medication (long-acting β2-agonist [LABA], leukotriene receptor antagonist [LTRA], theophylline, or long-acting muscarinic antagonist [LAMA]) steadily increased over time (2001 = 49.8%, 2017 = 68.3%). Of those prescribed their first preventer, one-third were prescribed a higher-level medication, of whom half had no reliever prescription or exacerbation in the year prior. Of patients first prescribed ICSs + 1 add-on, 70.4% remained on the same medication during a mean follow-up of 6.6 years. Of those prescribed medium/high-dose ICSs as their first preventer, 13.0% already had documented diabetes, cataracts, glaucoma, or osteopenia/osteoporosis. A cohort of 125,341 patients were drawn to assess the impact of stepping down medication: mean age 50.4 years, 39.4% males, 39,881 stepped down. Exposed patients were stepped down by dropping their LABAs or another add-on or by halving their ICS dose (halving their mean-daily dose or their inhaler dose). The primary and secondary outcomes were, respectively, exacerbations and an increase in reliever prescriptions. Multivariable regression was used to assess outcomes and determine the prognostic factors for initiating stepdown. There was no increased exacerbation risk for each possible medication stepdown (ad

Journal article

Bloom C, Douglas I, Usmani OS, Quint JKet al., 2020, Inhaled corticosteroid treatment regimens and health outcomes in a UK COPD population study [Corrigendum], The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 15, Pages: 869-869, ISSN: 1176-9106

Journal article

Sundaram V, Rothnie K, Bloom C, Zakeri R, Sahadevan J, Singh A, Nagai T, Potts J, Wedzicha J, Smeeth L, Simon D, Timmis A, Rajagopalan S, Quint JKet al., 2020, Impact of comorbidities on peak troponin levels and mortality in acute myocardial infarction, Heart, Vol: 106, Pages: 677-685, ISSN: 1355-6037

OBJECTIVES: To characterise peak cardiac troponin levels, in patients presenting with acute myocardial infarction (AMI), according to their comorbid condition and determine the influence of peak cardiac troponin (cTn) levels on mortality. METHODS: We included patients with the first admission for AMI in the UK. We used linear regression to estimate the association between eight common comorbidities (diabetes mellitus, previous angina, peripheral arterial disease, previous myocardial infarction (MI), chronic kidney disease (CKD), cerebrovascular disease, chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD)) and peak cTn. Peak cTn levels were adjusted for age, sex, smoking status and comorbidities. Logistic regression and restricted cubic spline models were employed to investigate the association between peak cTn and 180-day mortality for each comorbidity. RESULTS: 330 367 patients with ST elevation myocardial infarction and non-ST elevation myocardial infarction 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 with patients without the respective comorbidities (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 comorbidities did not change substantially after adjusting for peak cTn. In general, cTnI had a stronger association with mortality than cTnT. CONCLUSIONS: In this nationwide analysis of patients presenting with AMI, comorbidities 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 interpr

Journal article

Axson E, Sundaram V, Bloom C, Bottle R, Cowie M, Quint Jet al., 2020, Temporal trends in the incidence of heart failure among patients with COPD and its association with mortality, Annals of the American Thoracic Society, Vol: 17, Pages: 939-948, ISSN: 1546-3222

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. Be

Journal article

Bloom CI, Douglas I, Usmani OS, Quint JKet al., 2020, Inhaled corticosteroid treatment regimens and health outcomes in a UK COPD population study, The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 15, Pages: 701-710, ISSN: 1176-9106

Background: Inhaled corticosteroids (ICS) are a prevailing treatment option for COPD patients but recent guidelines have relegated their use predominantly to patients with frequent exacerbations. Yet large numbers of patients worldwide are currently treated with ICS-containing regimens. We wished to determine in routine clinical practice how common ICS withdrawal is and the differences in health outcomes between patients managed on ICS-containing and non-ICS containing regimens.Patients and Methods: COPD patients were identified from the UK primary care electronic healthcare records, between 2014 and 2018. Patients were grouped into three treatment regimens: long-acting beta-agonist (LABA) and inhaled corticosteroids (ICS), LABA and long-acting muscarinic antagonist (LAMA), and triple therapy (LABA, LAMA and ICS). Annual incidence of ICS withdrawal was measured. Multivariable logistic regression was used to identify patient factors associated with withdrawal. Multivariable Poisson regression was used to assess the association of exacerbations and hospitalised pneumonia between the ICS-containing regimens (LABA-ICS and triple therapy) and patients prescribed LABA-LAMA.Results: Of 117,046 patients, around three-quarters were prescribed ICS-containing inhalers but ICS withdrawal occurred annually in only approximately 2– 3% of patients. Exacerbations in the past year, but not a past history of pneumonia, were associated with ICS withdrawal. A total of 31,034 patients using three treatment regimens (LABA-ICS, LABA-LAMA or triple therapy) were assessed for their relative risk of exacerbations and pneumonia; the exacerbation risk was slightly lower in LABA-ICS users but the same in triple therapy users, as compared to LABA-LAMA users (LABA-ICS adjusted IRR=0.82 (95% CI 0.73– 0.93), triple adjusted IRR=0.99 (95% CI 0.88– 1.11)). There was no difference in the pneumonia risk (LABA-ICS adjusted IRR=0.96 (95% CI 0.71– 1.31), triple adjusted IRR=1.16 (

Journal article

Axson E, Ragutheeswaran K, Sundaram V, Bloom C, Bottle A, Cowie M, Quint Jet al., 2020, Hospitalisation and mortality in patients with comorbid COPD and heart failure: a systematic review and meta-analysis, Respiratory Research, Vol: 21, Pages: 1-13, ISSN: 1465-9921

BackgroundDiscrepancy exists amongst studies investigating the effect of comorbid heart failure (HF) on the morbidity and mortality of chronic obstructive pulmonary disease (COPD) patients.MethodsMEDLINE 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).ResultsTwenty-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.ConclusionsIn 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

Journal article

Axson EL, Sundaram V, Bloom CI, Bottle A, Cowie MR, Quint JKet al., 2020, The Effect of Unrecognised and Confirmed Heart Failure on Acute Exacerbations of Chronic Obstructive Pulmonary Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Sundaram V, Bloom C, Zakeri R, halcox J, cohen A, bowrin K, briere J-B, banerjee A, simon D, Cleland J, Rajagopalan S, Quint Jet al., 2019, Temporal trends in the incidence, treatment patterns, and outcomes of coronary artery disease and peripheral artery disease in the United Kingdom, 2006-2015, European Heart Journal, Vol: 41, Pages: 1636-1649, ISSN: 0195-668X

AimsMost reports estimating national incidence rates of coronary (CAD) and peripheral arterial disease (PAD) have focused on stable outpatients or acute or elective hospital admissions, but not on the overall burden of disease. In this study, we report the changing trends in the population-level incidence of CAD and PAD, respectively from 2006 to 2015, statin utilization for secondary prevention and survival outcomes using multiple nationally representative data sources from the UK (primary care encounters, hospital admissions, and procedure-level data).Methods and resultsA nationally representative study of linked primary and secondary care electronic health records of 4.6 million individuals from the UK. We calculated crude and standardized annual incidence rates separately for CAD and PAD. Statin use for secondary prevention, trends in annual major vascular event rates, and mortality between 2006 and 2015, were estimated for CAD and PAD, respectively. We identified 160 376 and 70 753 patients with incident CAD and PAD, respectively. The age- and sex-standardized incidence of CAD was similar in 2006 (443 per 100 000 person-years) and 2015 [436 per 100 000 person-years; adjusted incidence rate ratio (IRR) 0.98, 95% confidence interval (CI) 0.96–1.00]. In contrast, there was a 15% decline in the standardized incidence of PAD (236 per 100 000 person-years in 2006 to 202 per 100 000 person-years in 2015; adjusted IRR 0.85, 95% CI 0.82–0.88). The proportion of incident CAD and PAD patients prescribed long-term statins, was only 66% and 55%, respectively and was less common amongst women, patients aged >70 years, with heart failure, chronic lung disease, or depression. Cardiovascular mortality declined by 43% for incident CAD (adjusted IRR 0.57, 95% CI 0.50–0.64) between 2006 and 2015 but did not decline for incident PAD (adjusted IRR 0.84, 95% CI 0.70–1.00).Conclusion and relevanceIn the UK, the standardized incidence of CAD appears stable bu

Journal article

Sundaram V, Rothnie K, Bloom C, Zakeri R, Sahadevan J, singh A, Nagai T, Potts J, Wedzicha J, smeeth L, simon D, timmis A, Rajagopalan S, Quint Jet al., 2019, The impact of co-morbidities on peak troponin levels and mortality in acute myocardial infarction: A population based, nationwide study, Heart, ISSN: 1355-6037

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.

Journal article

Axson EL, Sundaram V, Bloom CI, Bottle A, Cowie MR, Quint JKet al., 2019, EFFECT OF INCIDENT HEART FAILURE ON SHORT- AND LONG-TERM MORTALITY OF COPD PATIENTS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A1-A2, ISSN: 0040-6376

Conference paper

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